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Liraglutide plus metformin may reduce type 2 diabetes risk after gestational diabetes
Adding liraglutide to metformin may help reduce the risk for developing type 2 diabetes vs. metformin alone for women with gestational diabetes, according to findings published in the Journal of Diabetes and its Complications.
“Gestational diabetes doesn’t go away after the baby is delivered. If a woman has gestational diabetes, they are at risk for type 2 diabetes,” Karen E. Elkind-Hirsch, MSc, PhD, director of metabolic research at Woman’s Hospital in Baton Rouge, Louisiana, told Healio. “These are women who are 20 to 30 years old who are going to have type 2 diabetes for a really long time and ... the longer you have it the more problems.”
Elkind-Hirsch and colleagues randomly assigned 153 women with a BMI of at least 25 kg/m2 who had been diagnosed with gestational diabetes to daily 1.8 mg liraglutide (Victoza, Novo Nordisk) together with 2,000 mg metformin or to 2,000 mg metformin only. The researchers recorded BMI, waist circumference, body weight, insulin secretion sensitivity index, fasting blood glucose, mean blood glucose, Matsuda insulin sensitivity index, triglycerides, HDL cholesterol, LDL cholesterol and oral glucose tolerance tests at baseline and at 40, 60 and 84 weeks.
At 84 weeks, participants assigned liraglutide and metformin experienced a 0.3 mmol/L reduction in fasting blood glucose vs. baseline while participants assigned metformin alone experienced an increase of 0.3 mmol/L (P = .005). In addition, compared with baseline, participants assigned liraglutide experienced a 0.62 mmol/L reduction in mean blood glucose while participants assigned metformin alone experienced a 0.01 mmol/L reduction (P = .011).
The researchers also found that participants assigned liraglutide and metformin were able to achieve a 1.3-point increase in glucose-stimulated insulin sensitivity index vs. baseline while participants assigned metformin alone saw their score drop by 0.1 (P = .029). Additionally, participants assigned liraglutide and metformin achieved a 171.4-point increase in insulin secretion sensitivity index while participants assigned metformin only experienced a 12-point increase (P = .042).
The researchers observed a 0.45 mmol/L reduction in triglycerides vs. baseline and a 0.84-point reduction in triglycerides to HDL cholesterol ratio vs. baseline for participants assigned liraglutide and metformin and a 0.13 mmol/L reduction in triglycerides (P = .046) and a 0.15-point reduction in triglycerides to HDL cholesterol ratio (P = .05) for those assigned metformin alone.
Participants assigned liraglutide and metformin reduced their baseline body weight by 7.2%, BMI by 3.4 kg/m2 and waist circumference by 6 cm at 84 weeks while participants assigned metformin alone reduced their baseline body weight by 3.1% (P = .04) BMI by 1 kg/m2 (P = .047) and waist circumference by 1.1 cm (P = .023).
The researchers also found that 38.5% of those assigned liraglutide and metformin reported an adverse event vs. 19% of those assigned metformin.
“We are trying to find what’s the best way to prevent the progression in this population. ... That’s where pharmacotherapy comes in,” Elkind-Hirsch said. “Ideally, you don’t want them on these medicines, you want them to change their lifestyle, but we’ve got to do something in that period right after childbirth where they’re so at risk.” – by Phil Neuffer
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Karen E. Elkind-Hirsch, MSc, PhD, can be reached at karen.elkind-hirsch@womans.org.
Disclosure: Novo Nordisk provided funding for this study. Elkind-Hirsch reports she has served on the advisory board of and received research grant support from AstraZeneca.
Perspective
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While hyperglycemia usually resolves relatively quickly in the postpartum period for most women with gestational diabetes, many will experience persistent postpartum hyperglycemia. The state of hyperglycemia varies in terms of severity. However, within 5 years, up to 50% of women who had gestational diabetes will develop type 2 diabetes.
Diet and exercise are recommended as the initial approach to manage postpartum diabetes risk, unfortunately, though, this does not work for a significant number of patients. Lifestyle modifications are challenging to maintain, particularly during the early busy years of motherhood. Accordingly, identifying additional strategies to reduce the risk for developing type 2 diabetes in this setting would be very important.
One strategy is initiating metformin therapy postpartum. However, even metformin therapy may not be adequate for some patients. The current study is innovative in that it evaluated the effect of metformin vs. metformin in combination with liraglutide in the postpartum setting. The combination demonstrated superior efficacy in terms of correcting the underlying metabolic status in patients with gestational diabetes in the postpartum setting over 84 weeks of therapy. Body weight and central adiposity also were reduced more than observed with metformin alone.
The results of this study would support approaching some patients — perhaps those who are perceived to be at the highest risk — more aggressively, early in the postpartum period, to reduce the risk for developing prediabetes or type 2 diabetes, rather than waiting for the type 2 diabetes to manifest before initiating therapy.
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