STANDARD MEDICATIONS FOR type 2 diabetes represent a trade-off between glucotoxicity and insulin toxicity. Insulin, TZDs, and SUs all increase insulin or its effect to reduce hyperglycemia. The effect of the increased insulin becomes clinically obvious as weight gain. The price of better glucose control has been higher insulin dosage, so there is no net benefit. These medications simply trade lower glucotoxicity for higher insulin toxicity.
Metformin and DPP-4 medications use mechanisms other than raising insulin to lower blood glucose. But they do not lower insulin either, so the result is neither weight gain nor weight loss. Reducing glucotoxicity while keeping insulin neutral produces minimal benefits. Clinically, these medications are weight neutral, but also neutral with regard to cardiovascular risk or benefits.
Meta-analyses reviewing all the available literature up to 2016, including twenty randomized controlled trials, could only conclude that “there is no significant evidence of long term efficacy of insulin on any clinical outcome in T2D (type 2 diabetes). A similar review in the Journal of the American Medical Association that included all relevant trials up to March 2016 found that none of the drug classes considered, including metformin, SUs, TZDs, and DPP-4 inhibitors, reduced cardiovascular disease or other complications. Importantly, these older medications did not reduce the hyperinsulinemia that is the root problem, or indeed, made it worse. Again, diabetes will continue unless we treat the root cause.
While the scientific evidence is crystal clear, diabetes guidelines are slow to reflect this new reality. Dr. Victor Montori of the Mayo Clinic discovered that 95 percent of published guidelines endorsed the use of diabetes drugs despite their nonexistent benefits. Why would you take medications that have no benefits? Worse, why would you take medications that have no benefits and make you fat?
The classic medical treatment, which relies almost exclusively on pharmaceuticals to reduce blood glucose, can therefore best be described as how not to treat type 2 diabetes. By contrast, newer agents, which can reduce both blood glucose and insulin levels, show proven benefits to reduce heart and kidney complications of type 2 diabetes. Nevertheless, these medications, while an important step forward, are clearly not the answer; they do not reverse the root cause of type 2 diabetes—our diet.