Chapter 56
Obesity and Diabetes — 15
Many of these are old, out of favor, or are not especially useful, but it gives a sense of how much attention has been paid to this condition. Only in recent times have we learned that one in four people with difficult-to-control type 2 diabetes has high levels of cortisol and may benefit from treatments such as mifepristone, the same medication used for emergency contraception. Note also that some diabetologists and endocrinologists devote their careers to it, alongside the primary care physicians who care for most with the disease.
Attempts to lose weight and improve nutrition and exercise, while important, will not typically achieve long-term normalization of glucose regulation (hemoglobin A1c). The classic first line of treatment, which also works to help prevent type 2 diabetes, is metformin, a well-tolerated, inexpensive, widely available drug. The mechanism for its benefit, as pointed out earlier, is elusive, but it has been shown to decrease liver production of glucose and improve muscle sensitivity to insulin. Unlike many of the drug classes on the list, metformin is not linked to risk of hypoglycemia.
Thinking as a cardiologist, there are only two classes of T2D drugs that should be given high priority because they not only markedly improve glucose control but also have been proven through large randomized trials to protect against heart attacks, strokes, and death. Those are the SGLT-2 inhibitors that block reabsorption of glucose in the kidney, facilitating its excretion in the urine, and the GLP-1 family of drugs. In fact, if it weren’t for the cost, a recent analysis suggested they should be first-line treatment, not metformin or lifestyle intervention. These two classes of drugs, as a consequence of reducing end-organ damage, increase life expectancy. The SGLT-2 inhibitors, offering about a 15 percent reduction of death in people with type 2 diabetes or heart failure, are also linked to fewer kidney stones, an age-related condition, and in the mouse model to enhance the elimination of senescent cells, extending lifespan.
It is another example of buying health span: expensive drugs with superior outcomes that outclass many low-cost, generic, “old” drugs. However, at the individual level, there is the potential for the patient to help drive the physician’s decision for treatment of choice, at least in individuals with health insurance, which generally covers these preferred agents. Since their mechanisms for achieving better glucose control are different and don’t overlap, it is not surprising that the combination of GLP-1 drugs and SGLT-2 inhibitors add to each other’s effects. They may even be synergistic—adding up to more than their sum for reducing heart disease. A meta-analysis of twelve randomized trials involving more than seventy-three thousand participants with type 2 diabetes showed additive benefit for the combination of these two drug classes to reduce heart and kidney disease. The economics cry out for attention. We have more than thirty million Americans diagnosed with type 2 diabetes, and the cost of their care annually exceeds $413 billion. That figure doesn’t include the approximately nine million people who have type 2 diabetes but remain undiagnosed.