Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study.
OBJECTIVE
Metformin was approved by the Food and Drug Administration in 1995 subject to the conduct of a randomized trial to evaluate the risk of lactic acidosis or other serious adverse events (SAEs) with this agent, under usual care conditions.


METHODS
The Comparative Outcomes Study of Metformin Intervention versus Conventional (COSMIC) Approach Study was a randomized, open-label, active-comparator, parallel-group, 1-year trial in type 2 diabetic patients suboptimally controlled on diet or sulfonylurea. Patients received metformin (n = 7,227) or other usual care treatments (n = 1,505). The primary end point was the incidence of SAEs, death, and hospitalization.


RESULTS
SAEs occurred in 10.3% (95% CI 9.6-11.1%) of the metformin group and in 11.0% (9.5-12.7%) of the usual care group (P = 0.431). Lactic acidosis did not occur. All-cause mortality (1.1% [0.9-1.4%] vs. 1.3% [0.8-2.0%], P = 0.596) and hospitalization (9.4% [8.8-10.1%] vs. 10.4% [8.9-12.1%], P = 0.229) were similar between groups.


CONCLUSIONS
The incidence of SAEs was similar between groups. Lactic acidosis was not observed. Metformin may be safely prescribed for type 2 diabetes if contraindications and warnings are respected. This study demonstrates the utility of large, simple trials for risk evaluation of treatments for common diseases.
Cryer
Dennis R
DR
Bristol-Myers Squibb Company, 777 Scudders Mill Rd., Plainsboro, NJ 08536, USA. dennis.cryer@bms.com
Nicholas
Savian P
SP
Henry
David H
DH
Mills
Donna J
DJ
Stadel
Bruce V
BV
D000140:Acidosis, Lactic / Q000453:epidemiology / Q000517:prevention & control; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin