There have been a number of new developments in the treatment of type 2 diabetes, and a question often asked is whether some of the type 2 therapies might be beneficial for people with type 1 diabetes. For example, several years ago, one of my patients with type 1 diabetes was having trouble with weight and with blood glucose control on a basal-bolus insulin combination. We added metformin, and his blood sugars appeared to get a bit better. Then we added exenatide (Byetta) before breakfast and dinner, and he started to get much better control, lost some weight, and felt much better.
The first thing to think about here is that there is nothing about having type 1 diabetes which inherently prevents one from having features of type 2. If we think about it, the prevalence of type 2 is about one tenth among all adults, and about one quarter among those age 65 and older. Features of insulin resistance – what has been called “metabolic syndrome” – are even more common. So, surely a substantial number of adults with type 1 will have features of type 2. In fact, the EURODIAB study, which followed more than 3000 people with type 1 diabetes, and the DCCT study of intensive control of more than 1000 people with type 1 diabetes, both found that features of type 2 diabetes and of metabolic syndrome such as weight gain, elevated triglycerides, and elevated blood pressure all track together.
Furthermore, many of the drugs used in treating type 2 diabetes work to lower the blood glucose level to some extent independent of insulin – and so we might wonder whether, regardless of the “type” of diabetes, they could have generally beneficial effect. What are some of the interesting potential approaches?
First, metformin. This is generally regarded as a basic treatment for type 2, and there have been a few studies of its use in type 1 diabetes going back a number of years. We are not at all certain how it acts. In the liver and in skeletal muscle, metformin has actions similar to those of insulin, and it appears to work in the gastrointestinal tract as well to increase production of a hormone called glucagon-like peptide-1 (GLP-1). GLP-1 stimulates insulin, suppresses the anti-insulin hormone glucagon, slows emptying of the stomach (for most people with diabetes, this is too rapid, so such an effect is useful in delaying the rise in blood glucose after a meal), and seems as well to suppress the appetite.
Although GLP-1 itself cannot be given as a treatment because it is rapidly cleared from the circulation, there are long-acting forms of GLP-1, including exenatide (Byetta and Bydureon), liraglutide (Victoza), albiglutide (Tanzeum), and dulaglutide (Trulicity). These medicines are increasingly being studied and used in type 2 diabetic people taking insulin, and in many studies are as effective as insulin itself. There are a few studies suggesting that they might be helpful in type 1 diabetes as well.
An even newer form of treatment is to give medicines which inhibit the kidneys’ reabsorption of glucose. In a healthy adult, almost 200 grams of glucose go through the kidneys every day – and it all is reabsorbed. In diabetes, with the higher blood glucose levels the transporter proteins that do this are even more active, so that more glucose can be reabsorbed. The new medicines block much of this activity, and people with type 2 diabetes taking canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance), and others in development tend to lose weight (the increased urine glucose could account for a 200 calorie per day energy deficit) and have lower blood pressure, as well as having a substantial reduction in blood glucose levels.
What happened with my patient? After about four months, even though he was happy with having lost weight and with his level of control, he began to notice frequent hypoglycemic episodes, despite our reducing his insulin doses. We discontinued metformin, as that had not seemed terribly effective. And after another few months, we stopped Byetta. He has continued to maintain his lower weight and excellent control for the past five years.
None of the “type 2” medicines will replace insulin for people with type 1 diabetes – and it would be very dangerous to try this, because of the risk of severely uncontrolled blood glucose if insulin levels fall too low. And there is a counterargument, that there is no point taking an extra medication just to be able to use a bit less insulin. As many people with type 1 diabetes are able to produce some insulin, if we can make this work more effectively it seems likely that a person’s own insulin would have desirable effects in lowering glucose levels. But we must realize the potential for adverse reactions to all medications. A reasonable approach will be to carefully do studies of all these medicines in people with type 1 diabetes – and to individualize, individualize, individualize.