Glucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction.

AIMS: To evaluate the effects of adding glucagon-like peptide-1 (GLP-1) analogue therapy to insulin on glycated hemoglobin (HbA1c), weight, insulin dosage, treatment satisfaction, and risk of hypoglycaemia. METHODS: Type 2 diabetes patients with insulin therapy receiving a GLP-1 analogue at 4 Swedish centers were studied. Hypoglycemia was evaluated using glucometers and patient self-report. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to evaluate treatment satisfaction. RESULTS: Among 65 patients studied, 4 discontinued therapy, none due to hypoglycemia, and there were no suspected severe adverse events. Among 61 patients who remained on therapy over a mean of 7.0 months, 40 were treated with liraglutide and 21 with exenatide. HbA1c decreased from a mean of 8.9% (82.4 mmol/mol) to 7.9% (71.9 mmol/mol) (p<0.001), weight decreased from 111.1 kg to 104.0 kg (p<0.001) and insulin doses were reduced from 91.1U to 52.2U (p<0.001). There was one patient with severe hypoglycemia. The mean number of asymptomatic hypoglycemia per patient and month, reported for the last month (0.085 below 4.0 mmol/l and 0 below 3.0 mmol/l) and documented symptomatic hypoglycemia (0.24 below 4.0 mmol/l and 0.068 below 3.0 mmol/l) was low. The DTSQc showed higher treatment satisfaction than with the previous regimen of 11.9 (scale -18 to +18 points, p<0.001). CONCLUSIONS: The addition of GLP-1 analogues to insulin in patients with type 2 diabetes is associated with reductions in HbA1c, weight, and insulin dose, along with a low risk of hypoglycemia and high treatment satisfaction.

Effects of insulin versus sulphonylurea on beta-cell secretion in recently diagnosed type 2 diabetes patients: a 6-year follow-up study.

BACKGROUND: Early insulin treatment is considered more beneficial than anti-diabetic medication with sulphonylureas, because the latter may exert negative effects on beta-cell function, while the former may help preserve it. In a previous study, we found that C-peptide response was increased in the insulin-treated group, whereas it was decreased in the glibenclamide group. However, it was not certain whether the advantage remained in the longer term. AIM: In this study, we tested whether early insulin treatment is more beneficial than glibenclamide against a 6-year follow-up perspective. METHODS: We designed a randomized clinical trial in subjects with newly diagnosed type 2 diabetes. Glucagon stimulatory tests, measuring C-peptide and islet amyloid polypeptide (IAPP), were performed after 2, and 3, days of temporary insulin and glibenclamide withdrawal. RESULTS: 18 subjects initially randomized to glibenclamide, and 16 randomized to two daily injections of insulin, participated in end-of-study investigations. C-peptide response to glucagon deteriorated (p < 0.01 vs. baseline) in initially glibenclamide-treated patients (n = 18), but not in insulin-treated patients (p < 0.05 for difference between groups, after 2 days of treatment withdrawal). The IAPP response to glucagon declined in the glibenclamide group (p < 0.001), but not in insulin-treated subjects (p = 0.05 for difference between groups). CONCLUSIONS: Early insulin treatment preserves beta-cell secretory function better than glibenclamide even in a 6-year perspective.

Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients.

OBJECTIVE: To evaluate whether treatment with insulin in recently diagnosed type 2 diabetes is advantageous compared with glibenclamide treatment. RESEARCH DESIGN AND METHODS: Beta-cell function, glycemic control, and quality of life were monitored over 2 years in 39 patients with islet cell antibody-negative type 2 diabetes diagnosed 0-2 years before inclusion in a Swedish multicenter randomized clinical trial. Patients were randomized to either two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide (3.5-10.5 mg daily). C-peptide-glucagon tests were performed yearly in duplicate after 2-3 days of temporary withdrawal of treatment. RESULTS: After 1 year the glucagon-stimulated C-peptide response was increased in the insulin-treated group by 0.14 +/- 0.08 nmol/l, whereas it was decreased by 0.12 +/- 0.08 nmol/l in the glibenclamide group, P < 0.02 for difference between groups. After 2 years, fasting insulin levels were higher after treatment withdrawal in the insulin-treated versus the glibenclamide-treated group (P = 0.02). HbA(1c) levels decreased significantly during the first year in both groups; however, at the end of the second year, HbA(1c) had deteriorated in the glibenclamide group (P < 0.01), but not in the insulin-treated group. The difference in evolution of HbA(1c) during the second year was significant between groups, P < 0.02. A questionnaire indicated no difference in well-being related to treatment. CONCLUSIONS: Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.