Research

Hormonal

Early combination therapy with metformin, a thiazolidinedione (TZD), and a GLP-1 receptor agonist (exenatide) is required to correct the multiple pathophysiological defects of type 2 diabetes and preserve beta-cell function, whereas sulfonylureas should be avoided due to progressive beta-cell failure.

If you have type 2 diabetes or pre-diabetes (IGT), waiting until your blood sugar is high to treat it is too late. The paper argues you should start a combination of lifestyle changes, metformin, a TZD (like pioglitazone), and a GLP-1 agonist (like exenatide) early. Avoid sulfonylureas as they harm your pancreas over time. The goal is to protect your beta-cells, not just lower a number.

GoodSupportsHIGH confidence
A treatment paradigm shift is recommended in which combination therapy is initiated with diet/exercise, metformin... a thiazolidinedione (TZD)... and exenatide... Sulfonylureas are not recommended because, after an initial improvement in glycemic control, they are associated with a progressive rise in A1C and progressive loss of beta-cell function.
Ralph A. DeFronzo · Diabetes · 2009

Why this rating

Based on a review of multiple prospective studies and clinical trials cited by the author, though it is a lecture/review rather than a single new RCT.

Source

From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus

Ralph A. DeFronzo · Diabetes · 2009

DOI 10.2337/db09-9028

narrative_reviewCited 2,984×
Read the paper
DOI resolved against Crossref · corpus check 2026-06-10

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