In the Journals

Adjunctive liraglutide improves glycemic response in type 2 diabetes after bariatric surgery

Adults with persistent or recurrent type 2 diabetes after bariatric surgery saw sustained reductions in body weight and HbA1c after 26 weeks of adjunctive liraglutide therapy when compared with similar patients assigned to placebo, according to findings from a randomized controlled trial published in The Lancet Diabetes & Endocrinology.

“Even after surgery, 37% to 70% of patients do not achieve diabetes remission and, of those who do, 21% to 43% relapse within 3 to 9 years,” Alexander Dimitri Miras, PhD, a senior clinical lecturer and consultant in endocrinology in the division of diabetes, endocrinology and metabolism at Imperial College London, and colleagues wrote in the study background. “Therefore, the management of persistent or recurrent type 2 diabetes after metabolic surgery represents a clinical challenge because, in the absence of randomized trials, available guidelines do not provide specific recommendations on the safety and efficacy of glucose-lowering medication after metabolic surgery.”

Miras and colleagues analyzed data from 80 adults who underwent Roux-en-Y gastric bypass or vertical sleeve gastrectomy and had persistent or recurrent type 2 diabetes (HbA1c 6.5%) at least 1 year after surgery, recruited from five hospitals in London as part of GRAVITAS, a trial designed to investigate the safety and efficacy of liraglutide (Victoza, Novo Nordisk) on glycemic control in patients who underwent bariatric surgery. Between January 2016 and May 2018, researchers randomly assigned participants to 1.8 mg once-daily liraglutide (n = 53; 38% men; median age, 55 years; median diabetes duration, 16.4 years) or placebo (n = 27; 48% men; median age, 57 years; median diabetes duration, 19.6 years) for 26 weeks, both given with a reduced-calorie diet. The goal for participants was a 500 kcal per day deficit from baseline energy intake, along with increased physical activity. Primary outcome was change in HbA1c from baseline to 26 weeks.

Within the cohort, 71 participants completed the study and were included in the principal complete-cases analysis.

In linear regression analysis, the estimated mean difference in HbA1c change from baseline to 26 weeks for patients assigned to liraglutide was –13.3 mmol/mol (–1.22%, 95% CI, –19.7 to –7) compared with patients assigned placebo. Results did not change in analyses stratified by surgery type, according to researchers.

“Significant improvements in HbA1c levels from baseline were already apparent at week 6 in the liraglutide group and plateaued by week 18,” the researchers wrote. “By contrast, we noted an increase in HbA1c in the placebo group, which was statistically significant at week 18 and week 26.”

The estimated mean difference in body weight change from baseline to 26 weeks for patients assigned to liraglutide was –4.23 kg (95% CI, –6.81 to –1.64) compared with patients assigned placebo, with results persisting in analyses stratified by surgery type.

Adverse events were similar in the liraglutide and placebo groups (45% vs. 41%, respectively) and were primarily gastrointestinal in nature. One patient in the placebo group died; the cause was considered unrelated to study treatment.

“Patients with a range of baseline characteristics were included, thus making our findings applicable to a wide population base,” the researchers wrote. “Our results emphasize the importance of multimodal interventions for this complex group of patients and suggest that surgical, medical, psychological and nutritional therapies could have an additive, if not synergistic, effect in patients with suboptimal responses to metabolic surgery.” – by Regina Schaffer

Disclosures: Miras reports he has received honoraria, advisory board contributions and research grant funding from AstraZeneca, Boehringer Ingelheim, Fractyl, Johnson & Johnson and Novo Nordisk. Please see the study for all other authors’ relevant financial disclosures.

Adults with persistent or recurrent type 2 diabetes after bariatric surgery saw sustained reductions in body weight and HbA1c after 26 weeks of adjunctive liraglutide therapy when compared with similar patients assigned to placebo, according to findings from a randomized controlled trial published in The Lancet Diabetes & Endocrinology.

“Even after surgery, 37% to 70% of patients do not achieve diabetes remission and, of those who do, 21% to 43% relapse within 3 to 9 years,” Alexander Dimitri Miras, PhD, a senior clinical lecturer and consultant in endocrinology in the division of diabetes, endocrinology and metabolism at Imperial College London, and colleagues wrote in the study background. “Therefore, the management of persistent or recurrent type 2 diabetes after metabolic surgery represents a clinical challenge because, in the absence of randomized trials, available guidelines do not provide specific recommendations on the safety and efficacy of glucose-lowering medication after metabolic surgery.”

Miras and colleagues analyzed data from 80 adults who underwent Roux-en-Y gastric bypass or vertical sleeve gastrectomy and had persistent or recurrent type 2 diabetes (HbA1c 6.5%) at least 1 year after surgery, recruited from five hospitals in London as part of GRAVITAS, a trial designed to investigate the safety and efficacy of liraglutide (Victoza, Novo Nordisk) on glycemic control in patients who underwent bariatric surgery. Between January 2016 and May 2018, researchers randomly assigned participants to 1.8 mg once-daily liraglutide (n = 53; 38% men; median age, 55 years; median diabetes duration, 16.4 years) or placebo (n = 27; 48% men; median age, 57 years; median diabetes duration, 19.6 years) for 26 weeks, both given with a reduced-calorie diet. The goal for participants was a 500 kcal per day deficit from baseline energy intake, along with increased physical activity. Primary outcome was change in HbA1c from baseline to 26 weeks.

Within the cohort, 71 participants completed the study and were included in the principal complete-cases analysis.

In linear regression analysis, the estimated mean difference in HbA1c change from baseline to 26 weeks for patients assigned to liraglutide was –13.3 mmol/mol (–1.22%, 95% CI, –19.7 to –7) compared with patients assigned placebo. Results did not change in analyses stratified by surgery type, according to researchers.

“Significant improvements in HbA1c levels from baseline were already apparent at week 6 in the liraglutide group and plateaued by week 18,” the researchers wrote. “By contrast, we noted an increase in HbA1c in the placebo group, which was statistically significant at week 18 and week 26.”

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The estimated mean difference in body weight change from baseline to 26 weeks for patients assigned to liraglutide was –4.23 kg (95% CI, –6.81 to –1.64) compared with patients assigned placebo, with results persisting in analyses stratified by surgery type.

Adverse events were similar in the liraglutide and placebo groups (45% vs. 41%, respectively) and were primarily gastrointestinal in nature. One patient in the placebo group died; the cause was considered unrelated to study treatment.

“Patients with a range of baseline characteristics were included, thus making our findings applicable to a wide population base,” the researchers wrote. “Our results emphasize the importance of multimodal interventions for this complex group of patients and suggest that surgical, medical, psychological and nutritional therapies could have an additive, if not synergistic, effect in patients with suboptimal responses to metabolic surgery.” – by Regina Schaffer

Disclosures: Miras reports he has received honoraria, advisory board contributions and research grant funding from AstraZeneca, Boehringer Ingelheim, Fractyl, Johnson & Johnson and Novo Nordisk. Please see the study for all other authors’ relevant financial disclosures.