Metformin and the sulphonylureas: the comparative risk

Area of Science:

• Pharmacology
• Internal Medicine
• Clinical Toxicology

Background:

• Sulfonylurea-induced hypoglycemia (SIH) and metformin-associated lactic acidosis (MALA) are significant adverse drug events.
• Previous literature indicated high mortality rates for MALA.

Purpose of the Study:

• To compare the mortality risks of SIH and MALA.
• To evaluate the safety profiles of sulfonylureas and metformin in non-insulin-dependent diabetics.

Main Methods:

• Literature review of SIH cases until December 1982.
• Analysis of MALA cases, including contraindications and drug overdosage.
• Comparative mortality risk analysis using data from the Swedish Adverse Drug Reactions Advisory Committee (SADRAC).

Main Results:

• 843 SIH cases (9% mortality) and 42 MALA cases (43% mortality) were identified.
• Most MALA cases had contraindications (e.g., renal impairment) or were due to overdose.
• No significant difference in mortality risk was found between MALA and glibenclamide-associated hypoglycemia (0.0240 vs. 0.0332 per 1,000 patient-years).
• Hypoglycemia incidence with glibenclamide was higher than lactic acidosis with metformin.

Conclusions:

• Sulfonylureas are not inherently safer than metformin.
• Both drug classes demand cautious prescription for non-insulin-dependent diabetics.
• Particular care is advised for elderly patients and those with renal or hepatic dysfunction.