Combination daytime chlorpropamide-metformin/bedtime insulin in the treatment of secondary failures in non insulin dependent diabetes.
OBJECTIVE
To determine the effectiveness of the combination therapy with daytime chlorpropamide-metformin and bedtime NPH insulin in the treatment of secondary failures in NIDDM and to study its effects on insulin secretion.


METHODS
Non randomized open study with a duration of two months. The patients were followed six months after ending the study.


METHODS
Department of Diabetes and Lipid Metabolism. Instituto Nacional de la Nutrición "Salvador Zubirán", Mexico City. CHARACTERISTICS OF THE PATIENTS: Nine patients (seven women and two men) were included. All had NIDDM and secondary failure to antidiabetic oral drugs. Their fasting plasma glucose was 14.5 +/- 2 mM/L and their HbA1c 13.37 +/- 2.9%. At the entry and at the end of the study a 5h-OGTT was done with assays of plasma glucose and C-peptide.


METHODS
Chlorpropamide (375 mg/day) plus metformin (1200 mg/day) and bedtime insulin (0.1 U/kg/day).


RESULTS
After two months on combination therapy, fasting plasma glucose and HbA1c levels were remarkably improved (decreases of 7.3 +/- 0.6 and 9.1 +/- 1.02 respectively, p less than 0.002). The insulin dose was small (6.77 +/- 2.09 U/day). Side effects were minimal and infrequent. During the 5h-OGTT, the mean glucose area under the curve also decreased. The insulin secretion did not change but the C-peptide/glucose ratio increased. At the end of the study, the insulin dose was tapered off and stopped when possible. The four patients with the best glycemic control during the study were able to suspend the bedtime insulin and maintain a good control six months after the insulin suspension.


CONCLUSIONS
The combination therapy is useful in the treatment of secondary failures in NIDDM: Its advantages are the very low mean daily insulin dose needed, the low incidence of side effects and, if a HbA1c less than 8.7% is achieved, the restoration of oral antidiabetic drugs efficacy. The very low insulin dose used in this study could be explained by complementary effects of metformin and bedtime insulin on hepatic glucose output and a putative decrease in peripheral resistance attributable both to sulfonylurea and metformin.
Aguilar
C A
CA
Departamento de Diabetes y Metabolismo de Lipidos, Instituto Nacional de la Nutrición Salvador Zubirán, México, D.F.
Wong
B
B
Gómez-Pérez
F J
FJ
Rull
J A
JA
D000328:Adult; D000368:Aged; D002747:Chlorpropamide / Q000008:administration & dosage* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged
D007328:Insulin; D008687:Metformin; D002747:Chlorpropamide