Repaglinide/troglitazone combination therapy: improved glycemic control in type 2 diabetes.

Abstract

. P.R., L.J., and R.R. are members of the Novo Nordisk Diabetes Expert Advisory Board, and P.R., L.J., S.S., and R.R. are recipients of Novo Nordisk honoraria.Abbreviations: ECG, electrocardiogram; FPG, fasting plasma glucose. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Repaglinide/Troglitazone Combination Therapy Improved glycemic control in type 2 diabetes O R I G I N A L A R T I C L EOBJECTIVE -This multicenter open-label clinical trial compared the efficacy and safety of repaglinide/troglitazone combination therapy, repaglinide monotherapy, and troglitazone monotherapy in type 2 diabetes that had been inadequately controlled by sulfonylureas, acarbose, or metformin alone.RESEARCH DESIGN AND METHODS -Patients with type 2 diabetes (n = 256) who had inadequate glycemic control (HbA 1c Ն7.0%) during previous monotherapy were randomly assigned to receive repaglinide (0.5-4.0 mg at meals), troglitazone (200-600 mg once daily), or a combination of repaglinide (1-4 mg at meals) and troglitazone (200-600 mg once daily). After a 4-6 week washout period, the trial assessed 22 weeks of treatment: 3 weeks (weeks 0-2) of forced titration, 11 weeks of fixed-dose treatment (weeks 3-13), and 8 weeks (weeks 14-21) of titration to maximum dose. E m e r g i n g T r e a t m e n t s a n d T e c h n o l o g i e s 980DIABETES CARE, VOLUME 23, NUMBER 7, JULY 2000 Study designForced titration: weeks 0-2. After a 4-to 6-week washout period when previous drug therapy was discontinued, patients received 0.5 mg repaglinide 0-30 min before each meal, or 200 mg troglitazone once daily, or a combination of both repaglinide (0.5 mg at meals) and troglitazone (200 mg once daily). The dose of repaglinide was increased to 1.0 mg at meals after 1 week (after week 0) and was further increased to 2.0 mg after 2 weeks of treatment. The dose of troglitazone was increased to 400 mg once daily after 2 weeks of treatment. Patients in the combination therapy group received 1.0 mg repaglinide and 200 mg troglitazone after 1 week (after week 0), 2.0 mg repaglinide and 200 mg troglitazone after 2 weeks, and 2.0 mg repaglinide and 400 mg troglitazone at the end of third week of treatment. Fixed-dose treatment: weeks 3-13. The dosage levels of all treatments were then maintained for 11 weeks from the beginning of week 3 until the end of week 13. However, the clinical trial protocol called for a reduction in dosage in the event of persistent levels of fasting plasma glucose (FPG) Ͻ80 mg/dl and/or repeated major hypoglycemia. Such dose reduction was to be achieved by reversing the last step of the dose increment schedule. FPG and HbA 1c levels were measured at weeks 0, 10, and 14, and circulating liver transaminase levels were measured at weeks 0, 4, 7, 10, and 14. Titration to maximum dose: weeks 14-21. After 14 weeks of treatment, FPG values were used to assess the need for further escalation of the dose. If the FPG value was Ͼ120 mg/dl, then the patient was titrated to...

Combination Therapy With Nateglinide and a Thiazolidinedione Improves Glycemic Control in Type 2 Diabetes

“…The additive glucose-lowering effect observed in this study has been demonstrated previously when thiazolidinediones have been combined with metformin, sulfonylureas, repaglinide, and insulin (11)(12)(13)(14). In addition, monotherapies with sulfonylureas and metformin can achieve comparable results to those seen in this combination study (19).…”

Rationale and options for combination therapy in the treatment of Type 2 diabetes

“…The thiazolidinediones, rosiglitazone and pioglitazone, do not stimulate insulin release or cause hypoglycaemia [18] making them potentially suitable candidates for combination therapy with insulin-secretion enhancers. Although troglitazone is no longer available, a combination study of troglitazone with nateglinide [38] and a similar study with repaglinide [39] both showed a reduction of HbA 1c of 1.7% which was greater than the reduction seen with the respective monotherapies in the same trials. Ongoing studies with newer, actually available glitazones will show if these previous effects are indicative of class action.…”

Presenting anti-diabetic plants in Iranian traditional medicine

“…It is a major health problem with increasing prevalence all over the world. It causes complications such as nephropathy, neuropathy, retinopathy and blindness and increases mortality rate (Atalay and Laaksonen, 2002;Memisogullari et al, 2003;Raskin et al, 2000).…”