1. These are uncertain times in the field of type 2 diabetes. New drugs keep arriving, but no one seems to know which are best. Even the proper target of treatment is now disputed. Just as guidelines began to push for lower HbA1c targets, their advice collided head-on with research suggesting that this may actually increase overall mortality. So where do we really stand?
2. First, the fuss over A1c is overblown. The ACCORD trial didn’t really prove that tight A1c control increased deaths, rather it proved that the methods they used to cut A1c did. These included drugs that increase weight and combinations that increase risk of hypoglycemic events. ACCORD’s real lesson is not that low A1c targets are bad per se, it’s that you should stop chasing them when cutting that extra 0.5% means adding risky drugs.
3. We would all benefit from worrying less about pushing our 7% A1c patients down to 6%, and more about getting our 9% A1c patients down to 8%.
4. Metformin is a fine drug. It avoids the cardiovascular effects and weight gain seen with so many diabetes drugs, hypoglycemia risk is minimal, the anti-glycemic effect matches most new, pricier drugs. For most patients, the only reason to consider other drugs is if metformin monotherapy fails to adequately control blood glucose.
5. Unfortunately, the reality is that one diabetes medication typically lowers A1c by about 1%, and many patients’ glycemia is too stubborn to be tackled through just one mechanism. If you need a 2% reduction, you probably need two drugs, and so on. Unless the patient has poor kidney function, one of these will be metformin.
6. The CDA 2008 guidelines advise combination therapy at A1c > 9.0%, but they shy away from picking favourites among the newer drugs. Your 2nd drug’s mechanism should differ from the first. Two drugs at submaximal doses generally work better than one at maximum dose.
7. In the average patient with eGFR > 60, the best two-drug combination for now is probably metformin with the DPP-4 inhibitor sitagliptin (Januvia). Sitagliptin is very new, but at least no major problems have emerged yet. That puts it ahead of rosiglitazone (Avandia), with its added risk of heart failure and suspected added risk of cardiovascular events. Pioglitazone (Actos) doesn’t seem to have adverse cardiac effects, though it shares the TZD class tendency to increase fracture risk.
8. Sulfonylureas have issues with weight gain and hypoglycemia. The best, for benefit vs risks, is probably gliclazide. But don’t give it with a DPP-4 inhibitor, as this combination is untested.
9. Incretin mimetics, which promote satiety, should be a good option in patients with BMI > 35. Exenatide (Byetta) gets fine reviews in the U.S. and Europe, where it’s been approved for years. It delivers decent glycemic control, and weight loss instead of weight gain.
10. But the real star in recent diabetes research isn’t a drug at all. The low glycemic index diet was once controversial, but today its former critics are running for cover. Properly followed, its effect on A1c is greater than any drug, and fast-acting too. It’s the only treatment that attacks the very roots of the disease. Plus, all the secondary effects are good for you. But then, if our patients could be easily persuaded to eat like this, there would be no diabetes epidemic.
