Insulin glargine in combination with nateglinide in people with Type 2 diabetes: a randomized placebo-controlled trial

• Published in: Diabetic medicine Vol. 24; no. 4; pp. 344 - 349
• Main Authors: Dashora, U. K., Sibal, L., Ashwell, S. G., Home, P. D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-2007; Blackwell
• Subjects: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Blood Glucose Self-Monitoring; Cyclohexanes - administration & dosage; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Drug Administration Schedule; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; Hypoglycemic Agents - administration & dosage; Insulin - administration & dosage; Insulin - analogs & derivatives; Insulin Glargine; Insulin, Long-Acting; Male; Medical sciences; Metformin - therapeutic use; Middle Aged; nateglinide; Phenylalanine - administration & dosage; Phenylalanine - analogs & derivatives; Time Factors; Type 2 diabetes; Endocrinopathy; Type 2 diabetes; Insulin glargine; Placebo; Randomised controlled trial; Metabolic diseases; Clinical trial; Nateglinide
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2007.02094.x

Objective  To determine the effect of adding nateglinide to therapy with insulin glargine in adults with Type 2 diabetes previously treated with insulin and with poor blood glucose control.
Research design and methods  In this 16‐week, double‐blind, placebo‐controlled study, people with Type 2 diabetes [n = 55, HbA1c 8.2 ± 1.0 (± sd)%, duration of diabetes 12.8 ± 6.0 years, duration of insulin treatment 6.0 ± 4.0 years] were transferred to single bedtime injection of insulin glargine for a titration period of 4 weeks, and then randomized to nateglinide or matching placebo before meals in addition to insulin glargine. Metformin was continued if taken. Doses of insulin and oral medication were titrated to protocol for the treatment period of 12 weeks.
Results  Baseline‐adjusted self‐monitored capillary blood glucose concentration at 12 weeks was significantly lower with nateglinide + insulin glargine compared with placebo + insulin glargine after breakfast [difference −2.3 (95% confidence interval −4.4, −0.2) mmol/l, P = 0.030], before lunch [−2.5 (−4.6, −0.3) mmol/l, P = 0.029], and after lunch [−2.3 (−4.3, −0.4) mmol/l, P = 0.021], but not at other times. Baseline‐adjusted HbA1c was not lower with nateglinide + insulin glargine as compared with placebo + insulin glargine [7.8 ± 1.4 vs. 8.3 ± 1.0%, difference −0.43 (−0.98, 0.12)%].
Conclusions  Addition of nateglinide before meals to once‐daily insulin glargine in people with long‐standing diabetes already requiring insulin therapy improves blood glucose control in the early part of the day after breakfast and lunch, but does not provide good control of blood glucose levels overall.