COMPARISON OF INSULIN WITH OR WITHOUT CONTINUATION OF ORAL HYPOGLYCEMIC AGENTS IN THE TREATMENT OF SECONDARY FAILURE IN NIDDM PATIENTS

OBJECTIVES - Optimal insulin regimens for non-insulin-dependent diabet es mellitus (NIDDM) patients with secondary failure are controversial. We evaluated the efficacy, side effects, and quality of life of patie nts receiving insulin either alone or in combination with their previo us oral hypoglycemic agents (OHAs). RESEARCH DESIGN AND METHODS - Fift y-three Chinese patients with NIDDM (mean age 53.9 +/- 12.6 years, dur ation of diabetes 9.0 +/- 4.9 years, body wt 60.4 +/- 13.3 kg with cor responding body mass index 24.2 +/- 4.3 kg/m(2), receiving the maximum dose of sulfonylurea and/or metformin) were confirmed to have OHA fai lure. Twenty-seven patients were randomized to continue OHAs and were given additional bedtime insulin (combination group); 26 patients were randomized to insulin therapy alone with twice-daily insulin (insulin group). insulin doses were increased incrementally, aiming at fasting plasma glucose (FPG) <7.8 mmol/l during a stabilization period of up to 8 weeks. Insulin dosage, body weight, glycemic control, and quality of life were assessed before and at 3 and 6 months after stabilizatio n. RESULTS - Both groups showed similar improvement of glycemic contro l. For the combination group, FPG decreased from 13.5 +/- 2.7 to 8.9 /- 3.0 mmol/l at 3 months (P < 0.0001) and to 8.6 +/- 2.5 mmol/l at 6 months (P < 0.0001). For the insulin group, FPG decreased from 13.5 +/ - 3.6 to 7.5 +/- 3.0 mmol/l at 3 months (P < 0.0001) and to 9.8 +/- 3. 5 mmol/l at 6 months (P < 0.0001). No significant differences were obs erved between the groups. Similarly, both groups had significant impro vement of fructosamine and glycosylated hemoglobin (HbA(1c)). Fructosa mine fell from a mean of 458 to 365 mu mol/l at 3 months (P < 0.0001) and to 371 mu mol/l at 6 months (P < 0.0001) and from 484 to 325 mu mo l/l at 3 months (P < 0.0001) and to 350 mu mol/l at 6 months (P < 0.00 01) for the combination and insulin groups, respectively. HbA(1c) decr eased from 10.2 to 8.4% at 3 months (P < 0.0001) and to 8.7% at 6 mont hs (P < 0.0001) in the combination group and from 10.7 to 7.8% at 3 mo nths (P < 0.0001) and to 8.4% at 6 months (P < 0.0001) in the insulin group. Despite similar improvement of glycemia, insulin requirements w ere very different. At 3 months, the combination group was receiving a mean of 14.4 U/day compared with 57.5 U/day in the insulin group (P < 0.0001). Similar findings were observed at 6 months (15.0 vs. 57.2 U/ day, P < 0.0001). Both groups gained weight. However, for the combinat ion group, weight gain was 1.6 +/- 1.8 kg at 3 months and 2.1 +/- 2.5 kg at 6 months (both P < 0.0001 vs. baseline), whereas for the insulin group, weight gain was 3.5 +/- 4.3 and 5.2 +/- 4.1 kg, respectively ( both P < 0.0001 vs, baseline). Weight gain was significantly greater i n the insulin group (P < 0.05 at 3 months, and P < 0.005 at 6 months). Fasting plasma triglyceride decreased in the insulin group (1.8 +/- 1 .0 to 1.4 +/- 0.8 mmol/l at 3 months [P < 0.005] and to 1.4 +/- 0.7 mm ol/l at 6 months [P < 0.02]) but not in the combination group, No chan ges were observed in total and high-density lipoprotein cholesterol. N o severe hypoglycemic reactions were recorded in either group. Mild re actions occurred with similar frequency in both groups. Well-being and quality of life improved significantly in both groups. The majority o f patients (82.7%) wanted to continue insulin beyond 6 months, irrespe ctive of the treatment group. CONCLUSIONS - In NIDDM patients with sec ondary OHA failure, therapy with a combination of OHAs and insulin and with insulin alone was equally effective and well tolerated. However, combination therapy was associated with a lower insulin dose and less weight gain. Combination treatment may be considered when OHA failure occurs as a potential intermediate stage before full insulin