Insulin as a First-Line Therapy in Type 2 Diabetes
Should the use of sulfonylureas be halted?
- Eberhard Standl, MD and
- Oliver Schnell, MD
- From the Munich Diabetes Research Institute, Munich, Germany
- Address correspondence and reprint requests to Eberhard Standl, Chairman, Munich Diabetes Research Institute, Kölner Pl.1, D-80804 Munich, Germany. E-mail: eberhard.standl{at}lrz.uni-muenchen.de
- ADA, American Diabetes Association
- DPP, dipeptidyl peptidase
- EASD, European Association for the Study of Diabetes
- ESC, European Society of Cardiology
- UKPDS, UK Prospective Diabetes Study
Because a tidal wave of type 2 diabetes is presently rolling on a global scale, owing to the ever-increasing prevalence of obesity along with overnutrition, increasing physical inactivity, and aging populations worldwide, the debate is still ongoing over the appropriate first-line therapy. Recently, the International Diabetes Federation and the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) suggested distinct treatment algorithms (Fig. 1) (1), which have sparked the discussion even further, although there is strong agreement that weight-regulating nutrition and a prudent lifestyle are the cornerstones of any treatment. Here, the pro and con discussion explores the use of insulin versus sulfonylureas as first-line pharmacotherapy.
HOW EFFECTIVE IS INSULIN AS A FIRST-LINE THERAPY?
Evidence base
The landmark UK Prospective Diabetes Study (UKPDS) has published evidence-based outcome results comparing the randomized addition of insulin or sulfonylurea treatment (with glibenclamide) to lifestyle therapy after diagnosis of type 2 diabetes (2). To make a long story short, no difference between these two treatment options was observed. Both gave a similar degree of (yet overall unsatisfactory) metabolic control long term and both reduced microvascular complications significantly, but failed to reduce macrovascular end points. Both therapies were burdened by significant weight gain and the risk of serious hypoglycemic episodes (2). These downsides appeared to be more marked with insulin therapy. So, based on these data, very little evidence exists that first-line insulin therapy is superior to sulfonylurea treatment, since no other long-term studies are available at present.
Limitations of present information
Insulin therapy in the UKPDS was not very well structured and was mainly based on long-acting insulin, which more or less has been abandoned. Newer concepts of insulin therapy have not been tested, e.g., combination therapies with intermediate-acting insulins or insulin analogs with flat action profile together with oral agents, in particular with metformin. Likewise, meal-related insulin strategies with short-acting insulins or insulin analogs have …
