Should we use aggressive medical treatment to stop the progression of diabetic retinopathy?

The Buzz: In type 2 diabetics, intensive glucose and lipid control (but not intensive BP control) prevents the progression of diabetic retinopathy (DR), but the approach may harm more patients than it benefits.
Citation: NEJM 363;3 July 15, 2010
Summary: As part of a sub-study of the large multi-center RCT ACCORD trial, researchers evaluated 10,251 diabetic patients randomly assigned to intensive (A1c < 6.0%) vs standard therapy (A1c < 7.0-7.9%), and were followed to monitor progression of DR, including the need for laser surgery or vitrectomy. Decreased rates of progression of DR were seen in the intensive glucose (7.3 vs 10.4%, P = 0.003) and lipid (6.5 vs 10.2%, P = 0.006) groups, but not the intensive BP group (10.4 vs 8.8%, P = 0.29). However, the trial was halted early, and a large portion of patients with higher LDL levels and alb/creat scores and lower visual acuity scores did not receive 4 year follow-up.

Commentary: These findings need to be interpreted in conjunction with the ACCORD trial, since DR is only one CV endpoint that is seen in diabetics.  In fact, the trial was stopped early when results suggested intensive glucose lowering was found to have no benefit in MI/CVA prevention and increased all-cause mortality. These findings were not replicated in the newer ADVANCE trial, which used different glucose lowering agents.  However, despite this newer trial and the benefit seen in DR, it is likely most prudent to maintain an A1c goal of 7.0-7.9%. In addition, this study suggests adding fenofibrate therapy to a statin may be useful to slow DR progression, particularly if the patient is male and has high trigylcerides or low HDL, as CV risk reduction with fenofibrate was found in these subsets.

By: Elizabeth Haskins, MD

Which oral medications are best for obese patients with DM2?

The Buzz: Multiple classes of oral diabetes medications are weight-neutral or even beneficial for weight loss.
Citation: "Managing Type 2 Diabetes: Balancing HbA1c and Body Weight " Postgrad Med  2010 May  122(3):106-117.
Summary: Attempts at managing type 2 diabetes in the obese are often sabotaged by weight gain as a side effect of therapy. Weight loss has been shown to improve insulin resistance, improve glycemic control, and decrease the need for medication. Appropriate choice of medications in this population can help minimize weight gain and perhaps lead to weight loss, thus improving glycemic control and hopefully leading to improvements in overall cardiovascular risk. This review revealed that the antihyperglycemic agents most likely to be weight neutral or to promote loss were the biguanides (e.g. metformin), α-glucosidase inhibitors (e.g. acarbose), incretin mimetics (e.g. exenatide), amylin mimetics (e.g. pramlintide), DPP4-inhibitors (e.g. sitagliptin/saxagliptin). In addition, providers may consider the use of orlistat and sibutramine to target weight loss as adjuncts to conventional antihyperglycemic therapies.

Commentary: Further studies are needed to determine if these effects will translate into clinically relevant improvements in CV outcomes.
By: Sue Kim MD