Liraglutide, a once‐daily human GLP‐1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD‐1 SU)

Abstract

AimTo compare the effects of combining liraglutide (0.6, 1.2 or 1.8 mg/day) or rosiglitazone 4 mg/day (all n ≥ 228) or placebo (n = 114) with glimepiride (2–4 mg/day) on glycaemic control, body weight and safety in Type 2 diabetes.MethodsIn total, 1041 adults (mean ± sd), age 56 ± 10 years, weight 82 ± 17 kg and glycated haemoglobin (HbA1c) 8.4 ± 1.0% at 116 sites in 21 countries were stratified based on previous oral glucose-lowering mono : combination therapies (30 : 70%) to participate in a five-arm, 26-week, double-dummy, randomized study.ResultsLiraglutide (1.2 or 1.8 mg) produced greater reductions in HbA1c from baseline, (−1.1%, baseline 8.5%) compared with placebo (+0.2%, P < 0.0001, baseline 8.4%) or rosiglitazone (−0.4%, P < 0.0001, baseline 8.4%) when added to glimepiride. Liraglutide 0.6 mg was less effective (−0.6%, baseline 8.4%). Fasting plasma glucose decreased by week 2, with a 1.6 mmol/l decrease from baseline at week 26 with liraglutide 1.2 mg (baseline 9.8 mmol/l) or 1.8 mg (baseline 9.7 mmol/l) compared with a 0.9 mmol/l increase (placebo, P < 0.0001, baseline 9.5 mmol/l) or 1.0 mmol/l decrease (rosiglitazone, P < 0.006, baseline 9.9 mmol/l). Decreases in postprandial plasma glucose from baseline were greater with liraglutide 1.2 or 1.8 mg [−2.5 to −2.7 mmol/l (baseline 12.9 mmol/l for both)] compared with placebo (−0.4 mmol/l, P < 0.0001, baseline 12.7 mmol/l) or rosiglitazone (−1.8 mmol/l, P < 0.05, baseline 13.0 mmol/l). Changes in body weight with liraglutide 1.8 mg (−0.2 kg, baseline 83.0 kg), 1.2 mg (+0.3 kg, baseline 80.0 kg) or placebo (−0.1 kg, baseline 81.9 kg) were less than with rosiglitazone (+2.1 kg, P < 0.0001, baseline 80.6 kg). Main adverse events for all treatments were minor hypoglycaemia (< 10%), nausea (< 11%), vomiting (< 5%) and diarrhoea (< 8%).ConclusionsLiraglutide added to glimepiride was well tolerated and provided improved glycaemic control and favourable weight profile.

Liraglutide reverses pronounced insulin-associated weight gain, improves glycaemic control and decreases insulin dose in patients with type 2 diabetes: a 26 week, randomised clinical trial (ELEGANT)

“…Interestingly, the amount of insulin-induced weight gain was not significantly related to the amount of liraglutide-induced weight loss. In contrast with the registration trials [10][11][12][13][14], weight loss with liraglutide was inversely related to BMI, with the greatest weight loss occurring in patients with a lower rather than a higher BMI.…”

“…Glucagon-like peptide-1 (GLP-1) analogues stimulate insulin secretion, suppress glucagon release, and reduce food intake, resulting in improved glycaemic control and weight loss in type 2 diabetes [9][10][11][12][13][14][15]. Addition of GLP-1 analogues to insulin therapy may thus be beneficial in reversing pronounced insulin-induced weight gain.…”

Effects of once‐weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity

“…No new safety concerns were identified, in line with other GLP‐1RAs and longer‐term semaglutide trials 6, 7, 40…”

“…GLP‐1 receptor agonists (RAs) have been shown to reduce body weight and blood glucose levels in people who are overweight or obese, with or without diabetes 6, 7, 8, 9, 10. Furthermore, activation of GLP‐1 receptors in the human brain helps to regulate appetite and food reward 11.…”

Efficacy of liraglutide therapy in Japanese type 2 diabetic patients insufficiently controlled with basal‐supported oral therapy

“…Its starting dose was 0.5 mg, the minimum dose of the tablet available in Japan. With the addition of glimepiride, liraglutide was decreased from 0.9 mg/day to 0.6 mg/day, on the basis of the findings in previous clinical trials, where two‐thirds of the maximum dose of liraglutide in combination with glimepiride was as effective as the maximum dose 15 . Glimepiride was titrated to target glycemic goal by 0.5∼1.0 mg/day.…”