Repaglinide Versus Metformin in Combination With Bedtime NPH Insulin in Patients With Type 2 Diabetes Established on Insulin/Metformin Combination Therapy

Abstract

OBJECTIVE -To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n ϭ 39) or metformin (dose unchanged) (n ϭ 41). Insulin dose was titrated at the clinician's discretion, aiming for a fasting blood glucose (FBG) Յ6.0 mmol/l. RESULTS -Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA 1c (Diabetes Control and Complications Trial-aligned assay, normal range 4.6 -6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P ϭ 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P ϭ 0.03; P ϭ 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 Ϯ 0.4 kg (means Ϯ SE) (P ϭ 0.01) versus 2.7 Ϯ 0.4 kg (P Ͻ 0.0001) (P ϭ 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 Ϯ 0.8 to 34.1 Ϯ 0.5 (P ϭ 0.01) with insulin/metformin but decreased from 32.5 Ϯ 0.9 to 29.1 Ϯ 1.3 (P Ͻ 0.002) with insulin/repaglinide. CONCLUSIONS -Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction.

Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes

“…In contrast, in obese patients with T2DM, Furlong et al demonstrated favourable fasting and postprandial plasma glucose levels (seven-point profile) and HbA 1c with metformin compared with repaglinide, both in combination with insulin (15). Compared with obese patients with T2DM, non-obese patients with T2DM are characterized by disproportional reduced insulin secretion (29).…”

“…On the day of investigation, all patients were served a standard fat-rich breakfast meal (total energy content 3515 kJ) with 54% fat (139 mg cholesterol; 50.4 g fat including saturated 28.8 g, monounsaturated 15.0 g and polyunsaturated fatty acids 2.8 g), 13% protein and 33% carbohydrates (meal ingredients: dark bread 50 g, white bread 60 g, butter 20 g, cheese (60% fat) 40 g, sausage 20 g, jam 30 g, whole milk 200 ml). The morning dose of the study medication was taken immediately before or during the test meal and the pre-lunch dose was postponed until after the investigation.…”

“…Numerous studies have compared the effect of different antihyperglycaemic treatment regimens on postprandial glucose metabolism in patients with T2DM (14)(15)(16)(17)(18). So far, however, only relatively few among these studies included data on postprandial lipidaemia (17,(19)(20)(21)(22)(23)(24)(25)(26) and most studies included mainly obese patients with T2DM (15,16,(18)(19)(20)(21)(22)(23)26). However, among Caucasian patients with T2DM, w15-20% are not obese (27) and compared with obese patients with T2DM, non-obese patients with T2DM have a similar risk of CVD (28), but are characterized by a more deficient insulin secretion and lesser degree of insulin resistance (29).…”

Common Medications Which Lead to Unintended Alterations in Weight Gain or Organ Lipotoxicity

“…& Meglitinides, repaglinide and nateglinide, have a similar mechanism of action as sulfonylureas; in that, they act by increasing insulin secretion by pancreatic beta-cells. When compared to insulin/metformin, 13 weeks of treatment with repaglinide was associated with greater weight gain of 2.7 ± 0.4 kg [23]. Patients receiving repaglinide experienced more weight gain compared to nateglinide (1.8 and 0.7 kg, respectively) after 16 weeks of treatment [24].…”

Comparison of Once-Daily Glargine Plus Sulfonylurea with Twice-Daily 70/30 Aspart Premix in Insulin-Naive Japanese Patients with Diabetes

“…Studies analyzing insulin combination therapy with metformin, thiazolidinedione glinides, and ␣-glucosidase inhibitors have generally reported improvement in glycemic control. [11][12][13][14][15][16][17] Metformin, glitazones, and glimepiride are reported to reduce insulin requirements in patients poorly controlled with insulin. [14][15][16][17] Combination of SU with premix insulin may increase the risk of severe hypoglycemia.…”