MONTREAL – Amid common patient concerns about weight gain in the treatment of hyperthyroidism, findings from a large study suggest the therapy with the most favorable survival rate – radioiodine – is not associated with an increased risk of weight gain or obesity.

“EGRET is the first large study using population-based linked community and hospital data to elucidate the long-term consequences of treatment modalities for hyperthyroidism,” said co-author Kristien Boelaert, MD, PhD, while presenting the research at the American Thyroid Association annual meeting.

“The administration of [radioiodine] for hyperthyroidism is associated with a survival benefit for patients with hyperthyroidism and is not associated with increased risks of becoming obese,” Dr. Boelaert, a professor of endocrinology and consultant endocrinologist with the Institute of Applied Health Research, University of Birmingham, England, told this news organization.

However, “overall, there was a nearly 10% risk of major adverse cardiac events [MACE] in patients with hyperthyroidism regardless of the treatment modality used,” she noted.

Commenting on the findings, Jonathon O. Russell, MD, said the study offers surprising – but encouraging – results.

The discovery that radioiodine shows no increase in weight gain “contradicts numerous previous studies which have consistently demonstrated weight gain following definitive radioiodine,” Dr. Russell told this news organization.

Overall, however, “these findings reinforce our knowledge that definitive treatment of an overactive thyroid leads to a longer life – even if there is some weight gain,” added Dr. Russell, who is chief of the Division of Head and Neck Endocrine Surgery at Johns Hopkins, Baltimore.
 

Hyperthyroidism associated with serious long-term cardiometabolic issues

Hyperthyroidism is associated with serious long-term cardiovascular and metabolic morbidity and mortality, and treatment is therefore essential. However, the swing to hypothyroidism that often occurs afterward commonly results in regaining the weight lost due to the hyperthyroidism, if not more, potentially leading to obesity and its attendant health risks.

To investigate those risks in relation to the three key hyperthyroidism treatments, the authors conducted the EGRET trial. They identified 62,474 patients in the United Kingdom population-based electronic health record database who had newly diagnosed hyperthyroidism and were treated with antithyroid drugs (73.4%), radioiodine (19.5%), or thyroidectomy (7.1%) between April 1997 and December 2015.

Exclusion criteria included those with less than 6 months of antithyroid drugs as the only form of treatment, thyroid cancer, or pregnancy during the first episode.

With a median follow-up of about 8 years, those who were treated with thyroidectomy had a significantly increased risk of gaining weight, compared with the general population (P < .001), and of developing obesity (body mass index > 30 kg/m2; P = .003), while the corresponding increases with antithyroid drugs and radioiodine were not significantly different, compared with the general population over the same period.

In terms of survival, with an average follow-up of about 11 years per person, about 14% of the cohort died, with rates of 14.4% in the antithyroid drug group, 15.8% in the radioiodine group, and 9.2% in the thyroidectomy group.

Mortality rates were further assessed based on an average treatment effects analysis in which the average change was estimated, compared with the index of antithyroid drugs – for instance, if all were treated instead with radioiodine. In that extension of life analysis, those treated with radioiodine could be expected to die, on average, 1.2 years later than those taking antithyroid drugs (P < .001), while those treated with thyroidectomy would be expected to die 0.6 years later, which was not statistically significant.

Using the same average treatment effects analysis, Dr. Boelaert noted, “we found a slightly increased risk of major adverse cardiovascular events following radioiodine, compared with antithyroid drugs; [however], the risk was very small and may not be clinically relevant.”

“Previous data from our and other groups have shown reduced risks of mortality and cardiovascular death following radioiodine-induced hypothyroidism, although this is not confirmed in all studies.”
 

Weight gain after hyperthyroid treatment drives concerns

The findings are important because weight gain associated with hyperthyroidism treatment is no small matter for many patients, even prompting a lack of adherence to therapy for some, despite its importance, Dr. Boelaert noted.

“Since the majority of patients lose weight as a consequence of being hyperthyroid, it can be expected that they will at least regain the lost weight and possibly even have a weight overshoot,” she explained. “Indeed, many patients are reluctant to accept definitive treatment with surgery or radioiodine out of fear of weight gain.”

“This may cause difficulties to some patients who occasionally may even stop taking antithyroid drugs to prevent this weight regain. Such lack of adherence may have dire consequences and is likely a contributing factor to the increased mortality in these patients,” she observed.

In a previous study of 1,373 patients, Dr. Boelaert and colleagues found that men treated for hyperthyroidism gained an average of 8.0 kg (17.6 lb), and women gained an average of 5.5 kg (12.1 lb).

Compared with the background population, men were significantly more likely to gain weight over the study period (odds ratio, 1.7; P < .001) as were women (OR, 1.3; P < .001). Also in that study, radioiodine was associated with greater weight gain (0.6 kg; P < .001), compared with antithyroid drug treatment alone.

Dr. Russell added that even when weight gain does occur, the payoff of having treated the potentially serious state of hyperthyroidism is a highly beneficial trade-off.

Ultimately, “the goal of treating any patient with Graves’ should be to get them to become hypothyroid as quickly as possible,” he said. “Patients have options, and all of these options can be safe in the right situation.”

“It is unrealistic to think that going from a hyperthyroid state to a low thyroid state will not result in weight gain for many patients,” Dr. Russell added. “But the key point is that overall health is better despite this weight gain.”

Dr. Boelaert has disclosed consulting fees paid to the University of Birmingham by Lilly and Eisai. Dr. Russell has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MONTREAL – Amid common patient concerns about weight gain in the treatment of hyperthyroidism, findings from a large study suggest the therapy with the most favorable survival rate – radioiodine – is not associated with an increased risk of weight gain or obesity.

“EGRET is the first large study using population-based linked community and hospital data to elucidate the long-term consequences of treatment modalities for hyperthyroidism,” said co-author Kristien Boelaert, MD, PhD, while presenting the research at the American Thyroid Association annual meeting.

“The administration of [radioiodine] for hyperthyroidism is associated with a survival benefit for patients with hyperthyroidism and is not associated with increased risks of becoming obese,” Dr. Boelaert, a professor of endocrinology and consultant endocrinologist with the Institute of Applied Health Research, University of Birmingham, England, told this news organization.

However, “overall, there was a nearly 10% risk of major adverse cardiac events [MACE] in patients with hyperthyroidism regardless of the treatment modality used,” she noted.

Commenting on the findings, Jonathon O. Russell, MD, said the study offers surprising – but encouraging – results.

The discovery that radioiodine shows no increase in weight gain “contradicts numerous previous studies which have consistently demonstrated weight gain following definitive radioiodine,” Dr. Russell told this news organization.

Overall, however, “these findings reinforce our knowledge that definitive treatment of an overactive thyroid leads to a longer life – even if there is some weight gain,” added Dr. Russell, who is chief of the Division of Head and Neck Endocrine Surgery at Johns Hopkins, Baltimore.
 

Hyperthyroidism associated with serious long-term cardiometabolic issues

Hyperthyroidism is associated with serious long-term cardiovascular and metabolic morbidity and mortality, and treatment is therefore essential. However, the swing to hypothyroidism that often occurs afterward commonly results in regaining the weight lost due to the hyperthyroidism, if not more, potentially leading to obesity and its attendant health risks.

To investigate those risks in relation to the three key hyperthyroidism treatments, the authors conducted the EGRET trial. They identified 62,474 patients in the United Kingdom population-based electronic health record database who had newly diagnosed hyperthyroidism and were treated with antithyroid drugs (73.4%), radioiodine (19.5%), or thyroidectomy (7.1%) between April 1997 and December 2015.

Exclusion criteria included those with less than 6 months of antithyroid drugs as the only form of treatment, thyroid cancer, or pregnancy during the first episode.

With a median follow-up of about 8 years, those who were treated with thyroidectomy had a significantly increased risk of gaining weight, compared with the general population (P < .001), and of developing obesity (body mass index > 30 kg/m2; P = .003), while the corresponding increases with antithyroid drugs and radioiodine were not significantly different, compared with the general population over the same period.

In terms of survival, with an average follow-up of about 11 years per person, about 14% of the cohort died, with rates of 14.4% in the antithyroid drug group, 15.8% in the radioiodine group, and 9.2% in the thyroidectomy group.

Mortality rates were further assessed based on an average treatment effects analysis in which the average change was estimated, compared with the index of antithyroid drugs – for instance, if all were treated instead with radioiodine. In that extension of life analysis, those treated with radioiodine could be expected to die, on average, 1.2 years later than those taking antithyroid drugs (P < .001), while those treated with thyroidectomy would be expected to die 0.6 years later, which was not statistically significant.

Using the same average treatment effects analysis, Dr. Boelaert noted, “we found a slightly increased risk of major adverse cardiovascular events following radioiodine, compared with antithyroid drugs; [however], the risk was very small and may not be clinically relevant.”

“Previous data from our and other groups have shown reduced risks of mortality and cardiovascular death following radioiodine-induced hypothyroidism, although this is not confirmed in all studies.”
 

Weight gain after hyperthyroid treatment drives concerns

The findings are important because weight gain associated with hyperthyroidism treatment is no small matter for many patients, even prompting a lack of adherence to therapy for some, despite its importance, Dr. Boelaert noted.

“Since the majority of patients lose weight as a consequence of being hyperthyroid, it can be expected that they will at least regain the lost weight and possibly even have a weight overshoot,” she explained. “Indeed, many patients are reluctant to accept definitive treatment with surgery or radioiodine out of fear of weight gain.”

“This may cause difficulties to some patients who occasionally may even stop taking antithyroid drugs to prevent this weight regain. Such lack of adherence may have dire consequences and is likely a contributing factor to the increased mortality in these patients,” she observed.

In a previous study of 1,373 patients, Dr. Boelaert and colleagues found that men treated for hyperthyroidism gained an average of 8.0 kg (17.6 lb), and women gained an average of 5.5 kg (12.1 lb).

Compared with the background population, men were significantly more likely to gain weight over the study period (odds ratio, 1.7; P < .001) as were women (OR, 1.3; P < .001). Also in that study, radioiodine was associated with greater weight gain (0.6 kg; P < .001), compared with antithyroid drug treatment alone.

Dr. Russell added that even when weight gain does occur, the payoff of having treated the potentially serious state of hyperthyroidism is a highly beneficial trade-off.

Ultimately, “the goal of treating any patient with Graves’ should be to get them to become hypothyroid as quickly as possible,” he said. “Patients have options, and all of these options can be safe in the right situation.”

“It is unrealistic to think that going from a hyperthyroid state to a low thyroid state will not result in weight gain for many patients,” Dr. Russell added. “But the key point is that overall health is better despite this weight gain.”

Dr. Boelaert has disclosed consulting fees paid to the University of Birmingham by Lilly and Eisai. Dr. Russell has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MONTREAL – Amid common patient concerns about weight gain in the treatment of hyperthyroidism, findings from a large study suggest the therapy with the most favorable survival rate – radioiodine – is not associated with an increased risk of weight gain or obesity.

“EGRET is the first large study using population-based linked community and hospital data to elucidate the long-term consequences of treatment modalities for hyperthyroidism,” said co-author Kristien Boelaert, MD, PhD, while presenting the research at the American Thyroid Association annual meeting.

“The administration of [radioiodine] for hyperthyroidism is associated with a survival benefit for patients with hyperthyroidism and is not associated with increased risks of becoming obese,” Dr. Boelaert, a professor of endocrinology and consultant endocrinologist with the Institute of Applied Health Research, University of Birmingham, England, told this news organization.

However, “overall, there was a nearly 10% risk of major adverse cardiac events [MACE] in patients with hyperthyroidism regardless of the treatment modality used,” she noted.

Commenting on the findings, Jonathon O. Russell, MD, said the study offers surprising – but encouraging – results.

The discovery that radioiodine shows no increase in weight gain “contradicts numerous previous studies which have consistently demonstrated weight gain following definitive radioiodine,” Dr. Russell told this news organization.

Overall, however, “these findings reinforce our knowledge that definitive treatment of an overactive thyroid leads to a longer life – even if there is some weight gain,” added Dr. Russell, who is chief of the Division of Head and Neck Endocrine Surgery at Johns Hopkins, Baltimore.
 

Hyperthyroidism associated with serious long-term cardiometabolic issues

Hyperthyroidism is associated with serious long-term cardiovascular and metabolic morbidity and mortality, and treatment is therefore essential. However, the swing to hypothyroidism that often occurs afterward commonly results in regaining the weight lost due to the hyperthyroidism, if not more, potentially leading to obesity and its attendant health risks.

To investigate those risks in relation to the three key hyperthyroidism treatments, the authors conducted the EGRET trial. They identified 62,474 patients in the United Kingdom population-based electronic health record database who had newly diagnosed hyperthyroidism and were treated with antithyroid drugs (73.4%), radioiodine (19.5%), or thyroidectomy (7.1%) between April 1997 and December 2015.

Exclusion criteria included those with less than 6 months of antithyroid drugs as the only form of treatment, thyroid cancer, or pregnancy during the first episode.

With a median follow-up of about 8 years, those who were treated with thyroidectomy had a significantly increased risk of gaining weight, compared with the general population (P < .001), and of developing obesity (body mass index > 30 kg/m2; P = .003), while the corresponding increases with antithyroid drugs and radioiodine were not significantly different, compared with the general population over the same period.

In terms of survival, with an average follow-up of about 11 years per person, about 14% of the cohort died, with rates of 14.4% in the antithyroid drug group, 15.8% in the radioiodine group, and 9.2% in the thyroidectomy group.

Mortality rates were further assessed based on an average treatment effects analysis in which the average change was estimated, compared with the index of antithyroid drugs – for instance, if all were treated instead with radioiodine. In that extension of life analysis, those treated with radioiodine could be expected to die, on average, 1.2 years later than those taking antithyroid drugs (P < .001), while those treated with thyroidectomy would be expected to die 0.6 years later, which was not statistically significant.

Using the same average treatment effects analysis, Dr. Boelaert noted, “we found a slightly increased risk of major adverse cardiovascular events following radioiodine, compared with antithyroid drugs; [however], the risk was very small and may not be clinically relevant.”

“Previous data from our and other groups have shown reduced risks of mortality and cardiovascular death following radioiodine-induced hypothyroidism, although this is not confirmed in all studies.”
 

Weight gain after hyperthyroid treatment drives concerns

The findings are important because weight gain associated with hyperthyroidism treatment is no small matter for many patients, even prompting a lack of adherence to therapy for some, despite its importance, Dr. Boelaert noted.

“Since the majority of patients lose weight as a consequence of being hyperthyroid, it can be expected that they will at least regain the lost weight and possibly even have a weight overshoot,” she explained. “Indeed, many patients are reluctant to accept definitive treatment with surgery or radioiodine out of fear of weight gain.”

“This may cause difficulties to some patients who occasionally may even stop taking antithyroid drugs to prevent this weight regain. Such lack of adherence may have dire consequences and is likely a contributing factor to the increased mortality in these patients,” she observed.

In a previous study of 1,373 patients, Dr. Boelaert and colleagues found that men treated for hyperthyroidism gained an average of 8.0 kg (17.6 lb), and women gained an average of 5.5 kg (12.1 lb).

Compared with the background population, men were significantly more likely to gain weight over the study period (odds ratio, 1.7; P < .001) as were women (OR, 1.3; P < .001). Also in that study, radioiodine was associated with greater weight gain (0.6 kg; P < .001), compared with antithyroid drug treatment alone.

Dr. Russell added that even when weight gain does occur, the payoff of having treated the potentially serious state of hyperthyroidism is a highly beneficial trade-off.

Ultimately, “the goal of treating any patient with Graves’ should be to get them to become hypothyroid as quickly as possible,” he said. “Patients have options, and all of these options can be safe in the right situation.”

“It is unrealistic to think that going from a hyperthyroid state to a low thyroid state will not result in weight gain for many patients,” Dr. Russell added. “But the key point is that overall health is better despite this weight gain.”

Dr. Boelaert has disclosed consulting fees paid to the University of Birmingham by Lilly and Eisai. Dr. Russell has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

WASHINGTON – The updated Moderna bivalent COVID-19 vaccine that targets the original virus and the Omicron variant was superior to the original COVID booster in adults aged 18 and older, new results indicate.

The bivalent booster was superior regardless of age and whether a person had previously been infected with SARS-CoV-2.

Additionally, no new safety concerns emerged.

Spyros Chalkias, MD, senior medical director of clinical development at Moderna, presented the data during an annual scientific meeting on infectious diseases.

In the phase 2/3 trial, participants received either 50 mcg of the bivalent vaccine mRNA-1273.214 (25 mcg each of the original Wuhan-Hu-1 and Omicron BA.1 spike mRNAs) or 50 mcg of the standard authorized mRNA-1273. The doses were given as second boosters in adults who had previously received a two-dose primary series and a first booster at least 3 months before.

The model-based geometric mean titers (GMTs) ratio of the enhanced booster compared with the standard booster was 1.74 (1.49-2.04), meeting the prespecified bar for superiority against Omicron BA.1.

In participants without prior SARS-CoV-2 infection who received updated booster doses and those who received standard boosters, the neutralizing antibody GMTs against Omicron BA.1 were 2372.4 and 1473.5, respectively.

Additionally, the updated booster elicited higher GMTs (727.4) than the standard booster (492.1) against Omicron subvariants BA.4/BA.5. Safety and reactogenicity were similar for both vaccine groups.

“By the end of this year, we expect to also have clinical trial data from our BA.4/BA.5 bivalent booster,” Dr. Chalkias said.

In the interim, the U.S. Food and Drug Administration recently granted emergency use authorization for Moderna’s BA.4/BA.5 Omicron-targeting bivalent COVID-19 booster vaccine in children and adolescents aged 6-17 years.

Pfizer/BioNTech also has recently issued an announcement that their COVID-19 booster, adapted for the BA.4 and the BA.5 Omicron subvariants, generated a strong immune response and was well tolerated in human tests.

Pfizer/BioNTech said data from roughly 80 adult patients showed that the booster led to a substantial increase in neutralizing antibody levels against the BA.4/BA.5 variants after 1 week.
 

Separate study of causes of severe breakthrough infections in early vaccine formulations

Though COVID vaccines reduce the incidence of severe outcomes, there are reports of breakthrough infections in persons who received the original vaccines, and some of these have been serious.

In a separate study, also presented at the meeting, researchers led by first author Austin D. Vo, BS, with the VA Boston Healthcare System, used data collected from Dec. 15, 2020, through Feb. 28, 2022, in a U.S. veteran population to assess those at highest risk for severe disease despite vaccination.

Results of the large, nationwide retrospective study were simultaneously published in JAMA Network Open.

The primary outcome was development of severe COVID, defined as a hospitalization within 14 days of a confirmed positive SARS-CoV-2 test, receipt of supplemental oxygen, mechanical ventilation, or death within 28 days.

Among 110,760 participants with severe disease after primary vaccination, 13% (14,690) were hospitalized with severe COVID-19 or died.

The strongest risk factor for severe disease despite vaccination was age, the researchers found.

Presenting author Westyn Branch-Elliman, MD, associate professor of medicine with VA Boston Healthcare System, said, “We found that age greater than 50 was associated with an adjusted odds ratio of 1.42 for every 5-year increase.”

To put that in perspective, she said, “compared to patients who are 45 to 50, those over 80 had an adjusted odds ratio of 16 for hospitalization or death following breakthrough infection.”

Priya Nori, MD, an infectious disease specialist at Montefiore Medical Center in New York, said in an interview that the evidence that age is a strong risk factor for severe disease – even after vaccination – confirms that attention should be focused on those in the highest age groups, particularly those 80 years and older.

Other top risk factors included having immunocompromising conditions; having received cytotoxic chemotherapy within 6 months (adjusted odds ratio, 2.69; 95% confidence interval, 2.25-3.21); having leukemias/lymphomas (aOR, 1.84; 95% CI, 1.59-2.14); and having chronic conditions associated with end-organ disease.

A version of this article first appeared on Medscape.com.

WASHINGTON – The updated Moderna bivalent COVID-19 vaccine that targets the original virus and the Omicron variant was superior to the original COVID booster in adults aged 18 and older, new results indicate.

The bivalent booster was superior regardless of age and whether a person had previously been infected with SARS-CoV-2.

Additionally, no new safety concerns emerged.

Spyros Chalkias, MD, senior medical director of clinical development at Moderna, presented the data during an annual scientific meeting on infectious diseases.

In the phase 2/3 trial, participants received either 50 mcg of the bivalent vaccine mRNA-1273.214 (25 mcg each of the original Wuhan-Hu-1 and Omicron BA.1 spike mRNAs) or 50 mcg of the standard authorized mRNA-1273. The doses were given as second boosters in adults who had previously received a two-dose primary series and a first booster at least 3 months before.

The model-based geometric mean titers (GMTs) ratio of the enhanced booster compared with the standard booster was 1.74 (1.49-2.04), meeting the prespecified bar for superiority against Omicron BA.1.

In participants without prior SARS-CoV-2 infection who received updated booster doses and those who received standard boosters, the neutralizing antibody GMTs against Omicron BA.1 were 2372.4 and 1473.5, respectively.

Additionally, the updated booster elicited higher GMTs (727.4) than the standard booster (492.1) against Omicron subvariants BA.4/BA.5. Safety and reactogenicity were similar for both vaccine groups.

“By the end of this year, we expect to also have clinical trial data from our BA.4/BA.5 bivalent booster,” Dr. Chalkias said.

In the interim, the U.S. Food and Drug Administration recently granted emergency use authorization for Moderna’s BA.4/BA.5 Omicron-targeting bivalent COVID-19 booster vaccine in children and adolescents aged 6-17 years.

Pfizer/BioNTech also has recently issued an announcement that their COVID-19 booster, adapted for the BA.4 and the BA.5 Omicron subvariants, generated a strong immune response and was well tolerated in human tests.

Pfizer/BioNTech said data from roughly 80 adult patients showed that the booster led to a substantial increase in neutralizing antibody levels against the BA.4/BA.5 variants after 1 week.
 

Separate study of causes of severe breakthrough infections in early vaccine formulations

Though COVID vaccines reduce the incidence of severe outcomes, there are reports of breakthrough infections in persons who received the original vaccines, and some of these have been serious.

In a separate study, also presented at the meeting, researchers led by first author Austin D. Vo, BS, with the VA Boston Healthcare System, used data collected from Dec. 15, 2020, through Feb. 28, 2022, in a U.S. veteran population to assess those at highest risk for severe disease despite vaccination.

Results of the large, nationwide retrospective study were simultaneously published in JAMA Network Open.

The primary outcome was development of severe COVID, defined as a hospitalization within 14 days of a confirmed positive SARS-CoV-2 test, receipt of supplemental oxygen, mechanical ventilation, or death within 28 days.

Among 110,760 participants with severe disease after primary vaccination, 13% (14,690) were hospitalized with severe COVID-19 or died.

The strongest risk factor for severe disease despite vaccination was age, the researchers found.

Presenting author Westyn Branch-Elliman, MD, associate professor of medicine with VA Boston Healthcare System, said, “We found that age greater than 50 was associated with an adjusted odds ratio of 1.42 for every 5-year increase.”

To put that in perspective, she said, “compared to patients who are 45 to 50, those over 80 had an adjusted odds ratio of 16 for hospitalization or death following breakthrough infection.”

Priya Nori, MD, an infectious disease specialist at Montefiore Medical Center in New York, said in an interview that the evidence that age is a strong risk factor for severe disease – even after vaccination – confirms that attention should be focused on those in the highest age groups, particularly those 80 years and older.

Other top risk factors included having immunocompromising conditions; having received cytotoxic chemotherapy within 6 months (adjusted odds ratio, 2.69; 95% confidence interval, 2.25-3.21); having leukemias/lymphomas (aOR, 1.84; 95% CI, 1.59-2.14); and having chronic conditions associated with end-organ disease.

A version of this article first appeared on Medscape.com.

WASHINGTON – The updated Moderna bivalent COVID-19 vaccine that targets the original virus and the Omicron variant was superior to the original COVID booster in adults aged 18 and older, new results indicate.

The bivalent booster was superior regardless of age and whether a person had previously been infected with SARS-CoV-2.

Additionally, no new safety concerns emerged.

Spyros Chalkias, MD, senior medical director of clinical development at Moderna, presented the data during an annual scientific meeting on infectious diseases.

In the phase 2/3 trial, participants received either 50 mcg of the bivalent vaccine mRNA-1273.214 (25 mcg each of the original Wuhan-Hu-1 and Omicron BA.1 spike mRNAs) or 50 mcg of the standard authorized mRNA-1273. The doses were given as second boosters in adults who had previously received a two-dose primary series and a first booster at least 3 months before.

The model-based geometric mean titers (GMTs) ratio of the enhanced booster compared with the standard booster was 1.74 (1.49-2.04), meeting the prespecified bar for superiority against Omicron BA.1.

In participants without prior SARS-CoV-2 infection who received updated booster doses and those who received standard boosters, the neutralizing antibody GMTs against Omicron BA.1 were 2372.4 and 1473.5, respectively.

Additionally, the updated booster elicited higher GMTs (727.4) than the standard booster (492.1) against Omicron subvariants BA.4/BA.5. Safety and reactogenicity were similar for both vaccine groups.

“By the end of this year, we expect to also have clinical trial data from our BA.4/BA.5 bivalent booster,” Dr. Chalkias said.

In the interim, the U.S. Food and Drug Administration recently granted emergency use authorization for Moderna’s BA.4/BA.5 Omicron-targeting bivalent COVID-19 booster vaccine in children and adolescents aged 6-17 years.

Pfizer/BioNTech also has recently issued an announcement that their COVID-19 booster, adapted for the BA.4 and the BA.5 Omicron subvariants, generated a strong immune response and was well tolerated in human tests.

Pfizer/BioNTech said data from roughly 80 adult patients showed that the booster led to a substantial increase in neutralizing antibody levels against the BA.4/BA.5 variants after 1 week.
 

Separate study of causes of severe breakthrough infections in early vaccine formulations

Though COVID vaccines reduce the incidence of severe outcomes, there are reports of breakthrough infections in persons who received the original vaccines, and some of these have been serious.

In a separate study, also presented at the meeting, researchers led by first author Austin D. Vo, BS, with the VA Boston Healthcare System, used data collected from Dec. 15, 2020, through Feb. 28, 2022, in a U.S. veteran population to assess those at highest risk for severe disease despite vaccination.

Results of the large, nationwide retrospective study were simultaneously published in JAMA Network Open.

The primary outcome was development of severe COVID, defined as a hospitalization within 14 days of a confirmed positive SARS-CoV-2 test, receipt of supplemental oxygen, mechanical ventilation, or death within 28 days.

Among 110,760 participants with severe disease after primary vaccination, 13% (14,690) were hospitalized with severe COVID-19 or died.

The strongest risk factor for severe disease despite vaccination was age, the researchers found.

Presenting author Westyn Branch-Elliman, MD, associate professor of medicine with VA Boston Healthcare System, said, “We found that age greater than 50 was associated with an adjusted odds ratio of 1.42 for every 5-year increase.”

To put that in perspective, she said, “compared to patients who are 45 to 50, those over 80 had an adjusted odds ratio of 16 for hospitalization or death following breakthrough infection.”

Priya Nori, MD, an infectious disease specialist at Montefiore Medical Center in New York, said in an interview that the evidence that age is a strong risk factor for severe disease – even after vaccination – confirms that attention should be focused on those in the highest age groups, particularly those 80 years and older.

Other top risk factors included having immunocompromising conditions; having received cytotoxic chemotherapy within 6 months (adjusted odds ratio, 2.69; 95% confidence interval, 2.25-3.21); having leukemias/lymphomas (aOR, 1.84; 95% CI, 1.59-2.14); and having chronic conditions associated with end-organ disease.

A version of this article first appeared on Medscape.com.

WASHINGTON – In the 25 years since the United States first launched its universal vaccinations program to protect children against chickenpox (varicella), the program has seen dramatic results, a data analysis indicates.

Results from 1995 – when universal vaccinations began – through 2019 were presented an annual scientific meeting on infectious diseases by Mona Marin, MD, a medical epidemiologist at the Centers for Disease Control and Prevention. Researchers analyzed published data and surveillance data reported to the CDC.
 

Deaths in under-20 group all but eliminated

It’s now rare for children to be hospitalized with chickenpox, and deaths from the infection in people younger than 20 have largely been eliminated. But benefits extend even further.

Immunocompromised people or pregnant women and infants too young to be vaccinated also benefited from the children’s immunizations.

Each year, about 3.8 million cases, 10,500 hospitalizations, and 100 deaths from chickenpox are prevented in the United States thanks to the vaccination program, Dr. Marin said.

Over 25 years, 91 million cases, 238,000 hospitalizations, and 1,933 – 2,446 deaths have been prevented.

However, chickenpox is still widespread in most of the world.
 

U.S. first with universal program

The disease was thought to be of little consequence, Dr. Marin said, until the mid-1950s after the first cases of fatal varicella in immunocompromised children revealed the virus’ lethal potential.

The United States was the first country to introduce a universal vaccination program, Dr. Marin said. At the time, it was a one-dose vaccine. Within the first 10 years of the one-dose program, declines in chickenpox cases, hospitalization, and death rates went from 71% to 90% in comparison with previous years. But health care leaders wanted to close the remaining gap and target transmission in schools.

“It was a burden the United States considered unacceptable,” Dr. Marin said.

The leaders had seen the control of measles and polio and wanted the same for chickenpox.
 

Two-dose vaccines started in 2007

In 2007, the current two-dose policy was introduced. Administration of the first dose is recommended at age 12–15 months, and the second at age 4–6 years. Vaccination is required before the children enter kindergarten.

Coverage was high – at least 90% – the study authors reported; the two-dose program further reduced the number, size, and duration of outbreaks. Over the 25 years, the proportion of outbreaks with fewer than 10 cases increased from 28% to 73%.

By 2019, incidence had dropped by 97%, hospitalizations were down by 94%, and deaths had dropped by 97%.

The biggest decline was seen in those younger than 20, who were born during the vaccination program. That group saw declines of 97% to 99% in cases, hospitalizations, and incidence compared with rates before vaccinations.

Dr. Marin says one dose of the vaccine is moderately effective in preventing all varicella (82%) and is highly effective in preventing severe varicella (more than 97%).

“The second dose adds 10% or more improved protection against all varicella,” she said.

But there have been gains beyond medical advances.

Researchers calculated the economic benefit and found a net savings of $23 billion in medical costs (which also factored in lost wages from parents staying home to care for sick children).
 

Jaw-dropping results

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that “as someone who is not a vaccinologist, the declines in deaths, let alone hospitalizations, were jaw-dropping. I hadn’t really seen a synthesis of the impact of one and two doses.”

She said the declines in zoster among young people were interesting. The big question, she said, is what impact this may have for shingles infections in middle-aged adults over time, since chickenpox and shingles are caused by the same virus.

Dr. Marrazzo also noted the economic savings calculations.

“It’s such a cheap intervention. It’s one of the best examples of how a simple vaccine can affect a cascade of events that are a result of chronic viral infection,” she said.

There are also messages for the current debates over COVID-19 vaccinations.

“For me, it is further evidence of the profound population-level effect safe vaccines can have,” Dr. Marrazzo said.

The authors and Dr. Marrazzo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

WASHINGTON – In the 25 years since the United States first launched its universal vaccinations program to protect children against chickenpox (varicella), the program has seen dramatic results, a data analysis indicates.

Results from 1995 – when universal vaccinations began – through 2019 were presented an annual scientific meeting on infectious diseases by Mona Marin, MD, a medical epidemiologist at the Centers for Disease Control and Prevention. Researchers analyzed published data and surveillance data reported to the CDC.
 

Deaths in under-20 group all but eliminated

It’s now rare for children to be hospitalized with chickenpox, and deaths from the infection in people younger than 20 have largely been eliminated. But benefits extend even further.

Immunocompromised people or pregnant women and infants too young to be vaccinated also benefited from the children’s immunizations.

Each year, about 3.8 million cases, 10,500 hospitalizations, and 100 deaths from chickenpox are prevented in the United States thanks to the vaccination program, Dr. Marin said.

Over 25 years, 91 million cases, 238,000 hospitalizations, and 1,933 – 2,446 deaths have been prevented.

However, chickenpox is still widespread in most of the world.
 

U.S. first with universal program

The disease was thought to be of little consequence, Dr. Marin said, until the mid-1950s after the first cases of fatal varicella in immunocompromised children revealed the virus’ lethal potential.

The United States was the first country to introduce a universal vaccination program, Dr. Marin said. At the time, it was a one-dose vaccine. Within the first 10 years of the one-dose program, declines in chickenpox cases, hospitalization, and death rates went from 71% to 90% in comparison with previous years. But health care leaders wanted to close the remaining gap and target transmission in schools.

“It was a burden the United States considered unacceptable,” Dr. Marin said.

The leaders had seen the control of measles and polio and wanted the same for chickenpox.
 

Two-dose vaccines started in 2007

In 2007, the current two-dose policy was introduced. Administration of the first dose is recommended at age 12–15 months, and the second at age 4–6 years. Vaccination is required before the children enter kindergarten.

Coverage was high – at least 90% – the study authors reported; the two-dose program further reduced the number, size, and duration of outbreaks. Over the 25 years, the proportion of outbreaks with fewer than 10 cases increased from 28% to 73%.

By 2019, incidence had dropped by 97%, hospitalizations were down by 94%, and deaths had dropped by 97%.

The biggest decline was seen in those younger than 20, who were born during the vaccination program. That group saw declines of 97% to 99% in cases, hospitalizations, and incidence compared with rates before vaccinations.

Dr. Marin says one dose of the vaccine is moderately effective in preventing all varicella (82%) and is highly effective in preventing severe varicella (more than 97%).

“The second dose adds 10% or more improved protection against all varicella,” she said.

But there have been gains beyond medical advances.

Researchers calculated the economic benefit and found a net savings of $23 billion in medical costs (which also factored in lost wages from parents staying home to care for sick children).
 

Jaw-dropping results

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that “as someone who is not a vaccinologist, the declines in deaths, let alone hospitalizations, were jaw-dropping. I hadn’t really seen a synthesis of the impact of one and two doses.”

She said the declines in zoster among young people were interesting. The big question, she said, is what impact this may have for shingles infections in middle-aged adults over time, since chickenpox and shingles are caused by the same virus.

Dr. Marrazzo also noted the economic savings calculations.

“It’s such a cheap intervention. It’s one of the best examples of how a simple vaccine can affect a cascade of events that are a result of chronic viral infection,” she said.

There are also messages for the current debates over COVID-19 vaccinations.

“For me, it is further evidence of the profound population-level effect safe vaccines can have,” Dr. Marrazzo said.

The authors and Dr. Marrazzo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

WASHINGTON – In the 25 years since the United States first launched its universal vaccinations program to protect children against chickenpox (varicella), the program has seen dramatic results, a data analysis indicates.

Results from 1995 – when universal vaccinations began – through 2019 were presented an annual scientific meeting on infectious diseases by Mona Marin, MD, a medical epidemiologist at the Centers for Disease Control and Prevention. Researchers analyzed published data and surveillance data reported to the CDC.
 

Deaths in under-20 group all but eliminated

It’s now rare for children to be hospitalized with chickenpox, and deaths from the infection in people younger than 20 have largely been eliminated. But benefits extend even further.

Immunocompromised people or pregnant women and infants too young to be vaccinated also benefited from the children’s immunizations.

Each year, about 3.8 million cases, 10,500 hospitalizations, and 100 deaths from chickenpox are prevented in the United States thanks to the vaccination program, Dr. Marin said.

Over 25 years, 91 million cases, 238,000 hospitalizations, and 1,933 – 2,446 deaths have been prevented.

However, chickenpox is still widespread in most of the world.
 

U.S. first with universal program

The disease was thought to be of little consequence, Dr. Marin said, until the mid-1950s after the first cases of fatal varicella in immunocompromised children revealed the virus’ lethal potential.

The United States was the first country to introduce a universal vaccination program, Dr. Marin said. At the time, it was a one-dose vaccine. Within the first 10 years of the one-dose program, declines in chickenpox cases, hospitalization, and death rates went from 71% to 90% in comparison with previous years. But health care leaders wanted to close the remaining gap and target transmission in schools.

“It was a burden the United States considered unacceptable,” Dr. Marin said.

The leaders had seen the control of measles and polio and wanted the same for chickenpox.
 

Two-dose vaccines started in 2007

In 2007, the current two-dose policy was introduced. Administration of the first dose is recommended at age 12–15 months, and the second at age 4–6 years. Vaccination is required before the children enter kindergarten.

Coverage was high – at least 90% – the study authors reported; the two-dose program further reduced the number, size, and duration of outbreaks. Over the 25 years, the proportion of outbreaks with fewer than 10 cases increased from 28% to 73%.

By 2019, incidence had dropped by 97%, hospitalizations were down by 94%, and deaths had dropped by 97%.

The biggest decline was seen in those younger than 20, who were born during the vaccination program. That group saw declines of 97% to 99% in cases, hospitalizations, and incidence compared with rates before vaccinations.

Dr. Marin says one dose of the vaccine is moderately effective in preventing all varicella (82%) and is highly effective in preventing severe varicella (more than 97%).

“The second dose adds 10% or more improved protection against all varicella,” she said.

But there have been gains beyond medical advances.

Researchers calculated the economic benefit and found a net savings of $23 billion in medical costs (which also factored in lost wages from parents staying home to care for sick children).
 

Jaw-dropping results

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that “as someone who is not a vaccinologist, the declines in deaths, let alone hospitalizations, were jaw-dropping. I hadn’t really seen a synthesis of the impact of one and two doses.”

She said the declines in zoster among young people were interesting. The big question, she said, is what impact this may have for shingles infections in middle-aged adults over time, since chickenpox and shingles are caused by the same virus.

Dr. Marrazzo also noted the economic savings calculations.

“It’s such a cheap intervention. It’s one of the best examples of how a simple vaccine can affect a cascade of events that are a result of chronic viral infection,” she said.

There are also messages for the current debates over COVID-19 vaccinations.

“For me, it is further evidence of the profound population-level effect safe vaccines can have,” Dr. Marrazzo said.

The authors and Dr. Marrazzo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Key clinical point: Lower serum bile acid levels (≤2.8 mmol/L) were an independent predictor of progression of diabetic kidney disease (DKD) to end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.

Major finding: Overall, 34.78% of patients progressed to ESRD during a median follow-up of 19.02 months, with lower levels of serum bile acids being independently associated with a higher risk for progression to ESRD (adjusted hazard ratio, 5.319; P = .027).

Study details: This was a retrospective cohort study including 184 patients with T2DM and biopsy-proven DKD.

Disclosures: This study was supported by the Health Commission of Sichuan Province Program. The authors declared no conflict of interests.

Source: Xiao X et al. Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease. Front Endocrinol (Lausanne). 2022;13:1026995  (Oct 7). Doi: 10.3389/fendo.2022.1026995.

Key clinical point: Lower serum bile acid levels (≤2.8 mmol/L) were an independent predictor of progression of diabetic kidney disease (DKD) to end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.

Major finding: Overall, 34.78% of patients progressed to ESRD during a median follow-up of 19.02 months, with lower levels of serum bile acids being independently associated with a higher risk for progression to ESRD (adjusted hazard ratio, 5.319; P = .027).

Study details: This was a retrospective cohort study including 184 patients with T2DM and biopsy-proven DKD.

Disclosures: This study was supported by the Health Commission of Sichuan Province Program. The authors declared no conflict of interests.

Source: Xiao X et al. Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease. Front Endocrinol (Lausanne). 2022;13:1026995  (Oct 7). Doi: 10.3389/fendo.2022.1026995.

Key clinical point: Lower serum bile acid levels (≤2.8 mmol/L) were an independent predictor of progression of diabetic kidney disease (DKD) to end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.

Major finding: Overall, 34.78% of patients progressed to ESRD during a median follow-up of 19.02 months, with lower levels of serum bile acids being independently associated with a higher risk for progression to ESRD (adjusted hazard ratio, 5.319; P = .027).

Study details: This was a retrospective cohort study including 184 patients with T2DM and biopsy-proven DKD.

Disclosures: This study was supported by the Health Commission of Sichuan Province Program. The authors declared no conflict of interests.

Source: Xiao X et al. Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease. Front Endocrinol (Lausanne). 2022;13:1026995  (Oct 7). Doi: 10.3389/fendo.2022.1026995.

Key clinical point: Sodium glucose cotransporter 2 inhibitors (SGLT2i) did not increase the risk for hospitalization for critical limb ischemia (CLI) and lower extremity amputation (LEA) in patients with type 2 diabetes (T2D) compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

Major finding: SGLT2i was not associated with a higher risk for hospitalization for CLI and LEA compared with either GLP-1RA (hazard ratio [HR] 1.13; 95% CI 0.77-1.65 and HR 1.27; 95% CI 0.63-2.55, respectively) or DPP4i (HR 1.06; 95% CI 0.75-1.50 and HR 0.80; 95% CI 0.42-1.53, respectively).

Study details: Findings are from a population-based retrospective cohort study that propensity score-matched patients with T2D who initiated SGLT2i (n = 13,378) and those who initiated GLP-1RA (n = 13,378).

Disclosures: This study was partly supported by the research grant from National Taiwan University Hospital Yunlin Branch and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

Source: Lee YC et al. Risk of major adverse limb events in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A population-based retrospective cohort study. Front Pharmacol. 2022;13:869804  (Sep 13). Doi: 10.3389/fphar.2022.869804

Key clinical point: Sodium glucose cotransporter 2 inhibitors (SGLT2i) did not increase the risk for hospitalization for critical limb ischemia (CLI) and lower extremity amputation (LEA) in patients with type 2 diabetes (T2D) compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

Major finding: SGLT2i was not associated with a higher risk for hospitalization for CLI and LEA compared with either GLP-1RA (hazard ratio [HR] 1.13; 95% CI 0.77-1.65 and HR 1.27; 95% CI 0.63-2.55, respectively) or DPP4i (HR 1.06; 95% CI 0.75-1.50 and HR 0.80; 95% CI 0.42-1.53, respectively).

Study details: Findings are from a population-based retrospective cohort study that propensity score-matched patients with T2D who initiated SGLT2i (n = 13,378) and those who initiated GLP-1RA (n = 13,378).

Disclosures: This study was partly supported by the research grant from National Taiwan University Hospital Yunlin Branch and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

Source: Lee YC et al. Risk of major adverse limb events in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A population-based retrospective cohort study. Front Pharmacol. 2022;13:869804  (Sep 13). Doi: 10.3389/fphar.2022.869804

Key clinical point: Sodium glucose cotransporter 2 inhibitors (SGLT2i) did not increase the risk for hospitalization for critical limb ischemia (CLI) and lower extremity amputation (LEA) in patients with type 2 diabetes (T2D) compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

Major finding: SGLT2i was not associated with a higher risk for hospitalization for CLI and LEA compared with either GLP-1RA (hazard ratio [HR] 1.13; 95% CI 0.77-1.65 and HR 1.27; 95% CI 0.63-2.55, respectively) or DPP4i (HR 1.06; 95% CI 0.75-1.50 and HR 0.80; 95% CI 0.42-1.53, respectively).

Study details: Findings are from a population-based retrospective cohort study that propensity score-matched patients with T2D who initiated SGLT2i (n = 13,378) and those who initiated GLP-1RA (n = 13,378).

Disclosures: This study was partly supported by the research grant from National Taiwan University Hospital Yunlin Branch and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

Source: Lee YC et al. Risk of major adverse limb events in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A population-based retrospective cohort study. Front Pharmacol. 2022;13:869804  (Sep 13). Doi: 10.3389/fphar.2022.869804

Key clinical point: Stringent management of blood pressure (BP) with amlodipine in addition to standard diabetes therapy significantly improved glycemic control in patients with type 2 diabetes  (T2D) compared with standard diabetes therapy alone.

Major finding: After 24 weeks, amlodipine plus standard diabetes therapy vs. standard diabetes therapy alone led to a significant reduction in the mean glycated hemoglobin level (6.62% vs 7.01%; P = .01), fasting plasma glucose level (122 vs 129 mg/dL; P < .001), systolic blood pressure (132 vs 143 mm Hg; P < .001), and diastolic blood pressure (78.9 vs 86.0 mm Hg; P < .001), with neural effects on the lipid profile and urinary albumin excretion.

Study details: Findings are from a prospective cohort study including 168 patients with newly diagnosed T2D who received amlodipine plus standard diabetes therapy (n = 87) or standard diabetes therapy alone (n = 81).

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Li JC et al. Antihypertensive treatment improves glycemic control in patients with newly diagnosed type 2 diabetes mellitus: A prospective cohort study. Front Endocrinol (Lausanne). 2022;13:935561  (Sep 9). Doi: 10.3389/fendo.2022.935561.

Key clinical point: Stringent management of blood pressure (BP) with amlodipine in addition to standard diabetes therapy significantly improved glycemic control in patients with type 2 diabetes  (T2D) compared with standard diabetes therapy alone.

Major finding: After 24 weeks, amlodipine plus standard diabetes therapy vs. standard diabetes therapy alone led to a significant reduction in the mean glycated hemoglobin level (6.62% vs 7.01%; P = .01), fasting plasma glucose level (122 vs 129 mg/dL; P < .001), systolic blood pressure (132 vs 143 mm Hg; P < .001), and diastolic blood pressure (78.9 vs 86.0 mm Hg; P < .001), with neural effects on the lipid profile and urinary albumin excretion.

Study details: Findings are from a prospective cohort study including 168 patients with newly diagnosed T2D who received amlodipine plus standard diabetes therapy (n = 87) or standard diabetes therapy alone (n = 81).

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Li JC et al. Antihypertensive treatment improves glycemic control in patients with newly diagnosed type 2 diabetes mellitus: A prospective cohort study. Front Endocrinol (Lausanne). 2022;13:935561  (Sep 9). Doi: 10.3389/fendo.2022.935561.

Key clinical point: Stringent management of blood pressure (BP) with amlodipine in addition to standard diabetes therapy significantly improved glycemic control in patients with type 2 diabetes  (T2D) compared with standard diabetes therapy alone.

Major finding: After 24 weeks, amlodipine plus standard diabetes therapy vs. standard diabetes therapy alone led to a significant reduction in the mean glycated hemoglobin level (6.62% vs 7.01%; P = .01), fasting plasma glucose level (122 vs 129 mg/dL; P < .001), systolic blood pressure (132 vs 143 mm Hg; P < .001), and diastolic blood pressure (78.9 vs 86.0 mm Hg; P < .001), with neural effects on the lipid profile and urinary albumin excretion.

Study details: Findings are from a prospective cohort study including 168 patients with newly diagnosed T2D who received amlodipine plus standard diabetes therapy (n = 87) or standard diabetes therapy alone (n = 81).

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Li JC et al. Antihypertensive treatment improves glycemic control in patients with newly diagnosed type 2 diabetes mellitus: A prospective cohort study. Front Endocrinol (Lausanne). 2022;13:935561  (Sep 9). Doi: 10.3389/fendo.2022.935561.

Key clinical point: Patients with type 2 diabetes mellitus (T2D) receiving metformin vs other antidiabetic drugs or placebo had a higher risk for gastrointestinal (GI) adverse events (AE) such as abdominal pain, nausea, and diarrhea, with the risk for bloating and diarrhea being higher with metformin immediate release (IR) vs extended release (XR).

Major finding: Patients treated with metformin vs. placebo or any other antidiabetic drug were at a significantly higher risk for abdominal pain (risk ratio [RR] 1.491; P = .0001), diarrhea (RR 2.445; P = .0001), and nausea (RR 1.641; P = .0004). The risks for bloating (coefficient −0.89; P = .76) and diarrhea (coefficient −0.344; P = .0437) were higher with metformin IR vs XR.

Study details: The data come from a meta-analysis of 71 randomized controlled trials including 55,042 patients with T2D who were randomly assigned to receive metformin or comparators.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Nabrdalik K et al. Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:975912 (Sep 14). Doi: 10.3389/fendo.2022.975912

Key clinical point: Patients with type 2 diabetes mellitus (T2D) receiving metformin vs other antidiabetic drugs or placebo had a higher risk for gastrointestinal (GI) adverse events (AE) such as abdominal pain, nausea, and diarrhea, with the risk for bloating and diarrhea being higher with metformin immediate release (IR) vs extended release (XR).

Major finding: Patients treated with metformin vs. placebo or any other antidiabetic drug were at a significantly higher risk for abdominal pain (risk ratio [RR] 1.491; P = .0001), diarrhea (RR 2.445; P = .0001), and nausea (RR 1.641; P = .0004). The risks for bloating (coefficient −0.89; P = .76) and diarrhea (coefficient −0.344; P = .0437) were higher with metformin IR vs XR.

Study details: The data come from a meta-analysis of 71 randomized controlled trials including 55,042 patients with T2D who were randomly assigned to receive metformin or comparators.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Nabrdalik K et al. Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:975912 (Sep 14). Doi: 10.3389/fendo.2022.975912

Key clinical point: Patients with type 2 diabetes mellitus (T2D) receiving metformin vs other antidiabetic drugs or placebo had a higher risk for gastrointestinal (GI) adverse events (AE) such as abdominal pain, nausea, and diarrhea, with the risk for bloating and diarrhea being higher with metformin immediate release (IR) vs extended release (XR).

Major finding: Patients treated with metformin vs. placebo or any other antidiabetic drug were at a significantly higher risk for abdominal pain (risk ratio [RR] 1.491; P = .0001), diarrhea (RR 2.445; P = .0001), and nausea (RR 1.641; P = .0004). The risks for bloating (coefficient −0.89; P = .76) and diarrhea (coefficient −0.344; P = .0437) were higher with metformin IR vs XR.

Study details: The data come from a meta-analysis of 71 randomized controlled trials including 55,042 patients with T2D who were randomly assigned to receive metformin or comparators.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Nabrdalik K et al. Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:975912 (Sep 14). Doi: 10.3389/fendo.2022.975912

Key clinical point: Patients with type 2 diabetes (T2D) who used metformin vs. sulfonylurea were at a significantly lower risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), but not Parkinson’s disease (PD) or mild cognitive impairment (MCI).

Major finding: The risk for all-cause dementia (hazard ratio [HR] 0.80; 95% CI 0.73-0.88), AD (HR 0.81; 95% CI 0.70-0.94), and VD (HR 0.79; 95% CI 0.63-1.00) was significantly lower in metformin vs sulfonylurea users, with no significant difference in the risk for PD and MCI.

Study details: Findings are from a new user active comparator study including 112,591 patients with T2D, of which 96,140 were new metformin users and 16,451 were new sulfonylurea users.

Disclosures: This study was supported by Janssen Pharmaceuticals. AJ Nevado-Holgado declared receiving funding from Janssen Pharmaceuticals and others. QS Li declared being an employee of Janssen Research & Development, Johnson & Johnson, or holding equity in Johnson & Johnson.

Source: Newby D et al. Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 2022;10(5):e003036 (Sep 15). Doi: 10.1136/bmjdrc-2022-003036

Key clinical point: Patients with type 2 diabetes (T2D) who used metformin vs. sulfonylurea were at a significantly lower risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), but not Parkinson’s disease (PD) or mild cognitive impairment (MCI).

Major finding: The risk for all-cause dementia (hazard ratio [HR] 0.80; 95% CI 0.73-0.88), AD (HR 0.81; 95% CI 0.70-0.94), and VD (HR 0.79; 95% CI 0.63-1.00) was significantly lower in metformin vs sulfonylurea users, with no significant difference in the risk for PD and MCI.

Study details: Findings are from a new user active comparator study including 112,591 patients with T2D, of which 96,140 were new metformin users and 16,451 were new sulfonylurea users.

Disclosures: This study was supported by Janssen Pharmaceuticals. AJ Nevado-Holgado declared receiving funding from Janssen Pharmaceuticals and others. QS Li declared being an employee of Janssen Research & Development, Johnson & Johnson, or holding equity in Johnson & Johnson.

Source: Newby D et al. Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 2022;10(5):e003036 (Sep 15). Doi: 10.1136/bmjdrc-2022-003036

Key clinical point: Patients with type 2 diabetes (T2D) who used metformin vs. sulfonylurea were at a significantly lower risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), but not Parkinson’s disease (PD) or mild cognitive impairment (MCI).

Major finding: The risk for all-cause dementia (hazard ratio [HR] 0.80; 95% CI 0.73-0.88), AD (HR 0.81; 95% CI 0.70-0.94), and VD (HR 0.79; 95% CI 0.63-1.00) was significantly lower in metformin vs sulfonylurea users, with no significant difference in the risk for PD and MCI.

Study details: Findings are from a new user active comparator study including 112,591 patients with T2D, of which 96,140 were new metformin users and 16,451 were new sulfonylurea users.

Disclosures: This study was supported by Janssen Pharmaceuticals. AJ Nevado-Holgado declared receiving funding from Janssen Pharmaceuticals and others. QS Li declared being an employee of Janssen Research & Development, Johnson & Johnson, or holding equity in Johnson & Johnson.

Source: Newby D et al. Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 2022;10(5):e003036 (Sep 15). Doi: 10.1136/bmjdrc-2022-003036

Key clinical point: Combination of saxagliptin with metformin, acarbose, or gliclazide modified release was safe and effective as an initial treatment option in patients with newly diagnosed type 2 diabetes (T2D) and poor glycemic control.

Major finding: At 24 weeks, the mean changes in glycated hemoglobin (A1c) levels were −2.9% (95% CI −3.1% to −2.8%), −2.6% (95% CI −2.8% to −2.5%), and −2.8% (95% CI −2.9% to −2.6%) in saxagliptin+metformin (Saxa+Met), saxagliptin+acarbose (Saxa+Aca), and saxagliptin+gliclazide (Saxa+Gli) groups, respectively. Overall, 84.9%, 74.7%, and 80.3% of participants achieved an A1c < 7.0% in Saxa+Met, Saxa+Aca, and Saxa+Gli groups, respectively (P = .05), with the rates of hypoglycemia being low across all groups.

Study details: Findings are from a 24-week, randomized clinical trial including 648 treatment-naive patients with T2D and high A1c level who were randomly assigned to receive Saxa+Met (n = 216), Saxa+Aca (n = 216), or Saxa+Gli (n = 216).

Disclosures: This study was funded by AstraZeneca Pharmaceutical Company. The authors declared no conflicts of interest.

Source: Chen X et al. Saxagliptin combined with additional oral antihyperglycemic agents in drug-naive diabetic patients with high glycosylated hemoglobin: A 24-week, multicenter, randomized, open-label, active parallel-controlled group clinical trial in China (SUCCESS). Diabetes Obes Metab. 2022 (Sep 13). Doi: 10.1111/dom.14873

Key clinical point: Combination of saxagliptin with metformin, acarbose, or gliclazide modified release was safe and effective as an initial treatment option in patients with newly diagnosed type 2 diabetes (T2D) and poor glycemic control.

Major finding: At 24 weeks, the mean changes in glycated hemoglobin (A1c) levels were −2.9% (95% CI −3.1% to −2.8%), −2.6% (95% CI −2.8% to −2.5%), and −2.8% (95% CI −2.9% to −2.6%) in saxagliptin+metformin (Saxa+Met), saxagliptin+acarbose (Saxa+Aca), and saxagliptin+gliclazide (Saxa+Gli) groups, respectively. Overall, 84.9%, 74.7%, and 80.3% of participants achieved an A1c < 7.0% in Saxa+Met, Saxa+Aca, and Saxa+Gli groups, respectively (P = .05), with the rates of hypoglycemia being low across all groups.

Study details: Findings are from a 24-week, randomized clinical trial including 648 treatment-naive patients with T2D and high A1c level who were randomly assigned to receive Saxa+Met (n = 216), Saxa+Aca (n = 216), or Saxa+Gli (n = 216).

Disclosures: This study was funded by AstraZeneca Pharmaceutical Company. The authors declared no conflicts of interest.

Source: Chen X et al. Saxagliptin combined with additional oral antihyperglycemic agents in drug-naive diabetic patients with high glycosylated hemoglobin: A 24-week, multicenter, randomized, open-label, active parallel-controlled group clinical trial in China (SUCCESS). Diabetes Obes Metab. 2022 (Sep 13). Doi: 10.1111/dom.14873

Key clinical point: Combination of saxagliptin with metformin, acarbose, or gliclazide modified release was safe and effective as an initial treatment option in patients with newly diagnosed type 2 diabetes (T2D) and poor glycemic control.

Major finding: At 24 weeks, the mean changes in glycated hemoglobin (A1c) levels were −2.9% (95% CI −3.1% to −2.8%), −2.6% (95% CI −2.8% to −2.5%), and −2.8% (95% CI −2.9% to −2.6%) in saxagliptin+metformin (Saxa+Met), saxagliptin+acarbose (Saxa+Aca), and saxagliptin+gliclazide (Saxa+Gli) groups, respectively. Overall, 84.9%, 74.7%, and 80.3% of participants achieved an A1c < 7.0% in Saxa+Met, Saxa+Aca, and Saxa+Gli groups, respectively (P = .05), with the rates of hypoglycemia being low across all groups.

Study details: Findings are from a 24-week, randomized clinical trial including 648 treatment-naive patients with T2D and high A1c level who were randomly assigned to receive Saxa+Met (n = 216), Saxa+Aca (n = 216), or Saxa+Gli (n = 216).

Disclosures: This study was funded by AstraZeneca Pharmaceutical Company. The authors declared no conflicts of interest.

Source: Chen X et al. Saxagliptin combined with additional oral antihyperglycemic agents in drug-naive diabetic patients with high glycosylated hemoglobin: A 24-week, multicenter, randomized, open-label, active parallel-controlled group clinical trial in China (SUCCESS). Diabetes Obes Metab. 2022 (Sep 13). Doi: 10.1111/dom.14873

Key clinical point: As an adjunct to metformin, bexagliflozin (20 mg) demonstrated antidiabetic potency equivalent to titrated glimepiride in patients with type 2 diabetes (T2D) inadequately controlled on metformin. Additional benefits were demonstrated in the form of weight loss, reduced systolic blood pressure (SBP), and fewer hypoglycemic events.

Major finding: At week 60, the least squares mean difference in glycated hemoglobin levels between bexagliflozin and glimepiride was −0.05% (95% CI −0.21% to 0.11%), showing noninferiority of bexagliflozin over glimepiride; however, bexagliflozin was superior to glimepiride for weight loss (P < .0001), decrease in SBP (P = .0008), and hypoglycemia incidence (P < .0001).

Study details: This 96-week randomized controlled trial included 426 patients with T2D (7.0% ≤ A1c ≤ 10.5%) inadequately controlled on metformin who were randomly assigned to receive bexagliflozin (n = 213) or titrated glimepiride (n = 213).

Disclosures: This study was funded by Theracos Sub, LLC. Some authors including the lead author were supported by a research grant to the Massachusetts General Hospital from Theracos Sub, LLC.

Source: Halvorsen YD et al. A 96-week, double-blind, randomized, controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2022 (Sep 30). Doi: 10.1111/dom.14875

Key clinical point: As an adjunct to metformin, bexagliflozin (20 mg) demonstrated antidiabetic potency equivalent to titrated glimepiride in patients with type 2 diabetes (T2D) inadequately controlled on metformin. Additional benefits were demonstrated in the form of weight loss, reduced systolic blood pressure (SBP), and fewer hypoglycemic events.

Major finding: At week 60, the least squares mean difference in glycated hemoglobin levels between bexagliflozin and glimepiride was −0.05% (95% CI −0.21% to 0.11%), showing noninferiority of bexagliflozin over glimepiride; however, bexagliflozin was superior to glimepiride for weight loss (P < .0001), decrease in SBP (P = .0008), and hypoglycemia incidence (P < .0001).

Study details: This 96-week randomized controlled trial included 426 patients with T2D (7.0% ≤ A1c ≤ 10.5%) inadequately controlled on metformin who were randomly assigned to receive bexagliflozin (n = 213) or titrated glimepiride (n = 213).

Disclosures: This study was funded by Theracos Sub, LLC. Some authors including the lead author were supported by a research grant to the Massachusetts General Hospital from Theracos Sub, LLC.

Source: Halvorsen YD et al. A 96-week, double-blind, randomized, controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2022 (Sep 30). Doi: 10.1111/dom.14875

Key clinical point: As an adjunct to metformin, bexagliflozin (20 mg) demonstrated antidiabetic potency equivalent to titrated glimepiride in patients with type 2 diabetes (T2D) inadequately controlled on metformin. Additional benefits were demonstrated in the form of weight loss, reduced systolic blood pressure (SBP), and fewer hypoglycemic events.

Major finding: At week 60, the least squares mean difference in glycated hemoglobin levels between bexagliflozin and glimepiride was −0.05% (95% CI −0.21% to 0.11%), showing noninferiority of bexagliflozin over glimepiride; however, bexagliflozin was superior to glimepiride for weight loss (P < .0001), decrease in SBP (P = .0008), and hypoglycemia incidence (P < .0001).

Study details: This 96-week randomized controlled trial included 426 patients with T2D (7.0% ≤ A1c ≤ 10.5%) inadequately controlled on metformin who were randomly assigned to receive bexagliflozin (n = 213) or titrated glimepiride (n = 213).

Disclosures: This study was funded by Theracos Sub, LLC. Some authors including the lead author were supported by a research grant to the Massachusetts General Hospital from Theracos Sub, LLC.

Source: Halvorsen YD et al. A 96-week, double-blind, randomized, controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2022 (Sep 30). Doi: 10.1111/dom.14875