Every year, the American Diabetes Association updates its “standards of medical care in diabetes.” The 2016 edition, which is 119 pages long, is available here. The most important part for type 2 diabetics is found on page 61, which has a chart showing the therapies used to treat diabetes.
First step is always metformin. Metformin is highly effective and low-risk, with side effects that are uncomfortable but typically not dangerous, like stomach pain, nausea, vomiting, or diarrhea. (Some patients, however, develop lactic acidosis.)
When another drug is added to metformin (called “dual therapy”), there are a variety of options, including insulin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors. Invokana is a SGLT-2 inhibitor. Januvia is a DPP-4 inhibitor.
SGLT-2 inhibitors like Invokana treat diabetes by acting on the kidneys, where they block the reabsorption of glucose, leading to less glucose in the blood. DPP-4 inhibitors treat diabetes by acting on the pancreas, where they help maintain higher levels of GLP-1, a hormone which triggers the production of insulin by the pancreas.
As the American Diabetes Association says, “Drug choice is based on patient preferences, as well as various patient, disease, and drug characteristics, with the goal of reducing blood glucose levels while minimizing side effects, especially hypoglycemia.” Obviously, you should discuss all of these issues with your doctor, and carefully consider their advice. But when it comes to the “patient preferences,” what should you know?
As the Invokana website points out, there was indeed a clinical trial where Invokana was shown to be modestly better than Januvia in reducing A1C levels. Similarly, a “retrospective matched-control cohort analysis” (a fancy name for going through medical records to look backwards to see how patients did) showed Invokana doing better in real-world applications. But the differences weren’t huge: both Invokana and Januvia users lowered their A1C levels by less than 1%. On a big statistical level, Invokana may be more effective, but the differences in a particular patient taking one or the other probably come down more to individual differences.
Moreover, we haven’t talked about one of the biggest issues: side effects. Both drugs have been linked to a large number of side effects.
Invokana has been linked with dehydration, kidney problems, yeast infections, ketoacidosis, and risks of bone fracture. Januvia has been linked with pancreatitis, changes in urination, skin reactions, and pancreatic cancer.
Truth is, we don’t know much about the long-term effects of Invokana and Januvia. Metformin has been approved for decades, and is currently being studied for its potential as an “anti-aging” medicine, given ample scientific data showing reduced cancer rates and benefits for cardiovascular disease and cognitive decline. In contrast, neither Invokana nor Januvia has been around long enough to see the full scope of effects on the body, including whether their “off-target” effects outside of diabetes may be harmful.