Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes.

Abstract

OBJECTIVE -To evaluate the efficacy and tolerability of nateglinide and metformin alone and in combination in type 2 diabetic patients inadequately controlled by diet, focusing on changes in HbA 1c , fasting plasma glucose (FPG), and mealtime glucose excursions.RESEARCH DESIGN AND METHODS -In this randomized double-blind study, patients with an HbA 1c level between 6.8 and 11.0% during a 4-week placebo run-in received 24 weeks' treatment with 120 mg nateglinide before meals (n = 179), 500 mg metformin three times a day (n = 178), combination therapy (n = 172), or placebo (n = 172). HbA 1c and FPG were evaluated regularly, and plasma glucose levels were determined after Sustacal challenge at weeks 0, 12, and 24. Hypoglycemia and other adverse events were recorded.RESULTS -At study end point, HbA 1c was reduced from baseline with nateglinide and metformin but was increased with placebo (Ϫ0.5, Ϫ0.8, and ϩ0.5%, respectively; P Յ 0.0001). Changes in FPG followed the same pattern (Ϫ0.7, Ϫ1.6, and ϩ0.4 mmol/l; P Յ 0.0001). Combination therapy was additive (HbA 1c Ϫ1.4% and FPG Ϫ2.4 mmol/l; P Յ 0.01 vs. monotherapy). After Sustacal challenge, there was a greater reduction in mealtime glucose with nateglinide monotherapy compared with metformin monotherapy or placebo (adjusted area under the curve [AUC] 0-130min Ϫ2.1, Ϫ1.1, and Ϫ0.6 mmol и h Ϫ1 и l Ϫ1 ; P Յ 0.0001). An even greater effect was observed with combination therapy (AUC 0-130min Ϫ2.5 mmol и h Ϫ1 и l Ϫ1 ; P Յ 0.0001 vs. metformin and placebo). All regimens were well tolerated.CONCLUSIONS -Nateglinide and metformin monotherapy each improved overall glycemic control but by different mechanisms. Nateglinide decreased mealtime glucose excursions, whereas metformin primarily affected FPG. In combination, nateglinide and metformin had complementary effects, improving HbA 1c , FPG, and postprandial hyperglycemia.

Beyond postprandial hyperglycaemia: metabolic factors associated with cardiovascular disease

“…The meglitinides for example have been shown to lower the post prandial glucose values in Type II diabetes by improving the insulin response to a meal. This resulted in a modest 0.5 to 0.6 % decline in HbA 1 c [141]. This observation is an important proof of concept, however, the long-term benefit remains to be established.…”

Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus

“…Related to this observation we found that patients treated with sulfonylureas had greater post-prandial blood glucose excursions than subjects not taking these medications, suggesting that sulfonylureas are not able to prevent postprandial glucose peaks. Patients taking sulfonylureas who have poor glycaemic control thus might benefit from therapy with glinides and short-acting insulin analogues to control post-prandial hyperglycaemia [40][41][42][43][44][45][46].…”

Postprandial blood glucose as a risk factor for cardiovascular disease in Type II diabetes: the epidemiological evidence

“…In other words, the goal of diabetes care should be the attainment of a more physiological glucose profile, and not only satisfactory levels of FPG or HbA 1 c . In this regard, the diabetes care provider might consider the use of oral hypoglycaemic agents that are specifically effective on postprandial hyperglycaemia, like new non-sulphonylureic insulin secretagogues [69,70]. These drugs have the specific ability to improve or even normalize the abnormal first-phase insulin secretion of Type II diabetic patients, thereby blunting the exaggerated glucose increase occurring after meals.…”