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Comparing Medications for Adults With Type 2 Diabetes

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Adverse Events and Side Effects: Comparisons of Two-Drug Combination Therapies

Hypoglycemia
There was high strength of evidence to conclude that the risk of hypoglycemia with metformin plus sulfonylurea is about six times as high as the risk of metformin plus thiazolidinediones. Moderate-grade evidence showed that metformin with a sulfonylurea has a higher risk of hypoglycemia than metformin with liraglutide (GLP-1 agonist). Moderate-grade evidence showed a modestly lower risk of hypoglycemia when metformin was combined with a basal insulin rather than a premixed insulin.

Gastrointestinal (GI) Side Effects
Moderate strength of evidence suggested that a combination of metformin and sulfonylurea is associated with higher rates of diarrhea compared with a combination of a thiazolidinedione and a sulfonylurea.

Hip and nonhip Fractures
High strength of evidence showed that thiazolidinediones, either in combination with another medication or as monotherapy, are associated with a higher risk of bone  fractures compared with metformin alone or in combination with sulfonylurea.