Glucose-Lowering Effects and Low Risk of Hypoglycemia in Patients With Maturity-Onset Diabetes of the Young When Treated With a GLP-1 Receptor Agonist: A Double-Blind, Randomized, Crossover Trial

Abstract

OBJECTIVEThe most common form of maturity-onset diabetes of the young (MODY), hepatocyte nuclear factor 1a (HNF1A diabetes: MODY3) is often treated with sulfonylureas that confer a high risk of hypoglycemia. We evaluated treatment with GLP-1 receptor agonists (GLP-1RAs) in patients with HNF1A diabetes. RESEARCH DESIGN AND METHODSSixteen patients with HNF1A diabetes (8 women; mean age 39 years [range 23-67 years]; BMI 24.9 6 0.5 kg/m 2 [mean 6 SEM]; fasting plasma glucose [FPG] 9.9 6 0.9 mmol/L; HbA 1c 6.4 6 0.2% [47 6 3 mmol/mol]) received 6 weeks of treatment with a GLP-1RA (liraglutide) and placebo (tablets), as well as a sulfonylurea (glimepiride) and placebo (injections), in randomized order, in a double-blind, crossover trial. Glimepiride was up-titrated once weekly in a treat-to-target manner; liraglutide was up-titrated once weekly to 1.8 mg once daily. At baseline and at the end of each treatment period a standardized liquid meal test was performed, including a 30-min light bicycle test. RESULTSFPG decreased during the treatment periods (21.6 6 0.5 mmol/L liraglutide [P = 0.012] and 22.8 6 0.7 mmol/L glimepiride [P = 0.003]), with no difference between treatments (P = 0.624). Postprandial plasma glucose (PG) responses (total area under the curve) were lower with both glimepiride (2,136 6 292 min 3 mmol/L) and liraglutide (2,624 6 340 min 3 mmol/L) compared with baseline (3,127 6 291 min 3 mmol/L; P < 0.001, glimepiride; P = 0.017, liraglutide), with no difference between treatments (P = 0.121). Eighteen episodes of hypoglycemia (PG £3.9 mmol/L) occurred during glimepiride treatment and one during liraglutide treatment. CONCLUSIONSSix weeks of treatment with glimepiride or liraglutide lowered FPG and postprandial glucose excursions in patients with HNF1A diabetes. The glucose-lowering effect was greater with glimepiride at the expense of a higher risk of exclusively mild hypoglycemia.

Liraglutide reduces the body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients

“…Liraglu-www.chinaphar.com Feng P et al Acta Pharmacologica Sinica npg tide, a GLP-1 receptor activator, has proven to be efficient for glycemic control in type 2 diabetic patients both in China and throughout the world [7,8] . Liraglutide is effective in patients with maturity-onset diabetes of the young (MODY) 3, and produces lower hypoglycemic risk than glimepiride [9] . Moreover, liraglutide has also been used as an anti-obesity therapy [10] .…”

Postprandial incretin and islet hormone responses and dipeptidyl-peptidase 4 enzymatic activity in patients with maturity onset diabetes of the young

“…Hyperglucagonaemia and increased DPP4 activity in MODY3 may represent relevant therapeutic targets (51) for drugs with glucagon-lowering and/or DPP4-inhibiting properties. Interestingly, very recent data from our group demonstrated a glucose-lowering effect on both FPG and postprandial PG during treatment with a GLP1 receptor agonist, but no significant effect on postprandial glucagon responses was demonstrated (51).…”

Maturity onset diabetes of the young: Diagnosis and treatment options

“…Other medications can also be useful, for instance glucagonlike peptide-1 receptor agonists, dipeptidyl peptidase IV inhibitors, meglitinide analogues showed excellent results in controlling glucose levels as well [70][71][72][73].…”