Sometimes, diabetes science confuses me.
Let's take the news of an emerging class of diabetes drugs (type 2-focused) that apparently do something we've always thought was bad... but it's actually not.
Sodium-glucose transporter (SGLT-2) inhibitors increase insulin production and effectiveness and stop the liver from producing too much glucose. Basically, they work by spilling glucose over into the urine which leads to less sugar in your bloodstream. The effect: lower BGs and A1Cs.
I may be scratching my head, but researchers and scientists are apparently singing the praises of this new wave of treatment, and pharmaceutical companies are jumping on the chance to develop these potentially profitable drugs.
Upcoming SGLT-2 inhibitors were a highlight at the American Diabetes Association's Scientific Sessions this year, with research presented and the medical community taking up the topic in a variety of sessions.
I sat in on some, and yes, there were a whole bunch of scientific terms and equations that took me back to 9th grade chemistry and science, when the periodic table used to give me nightmares.
But what I took away from the research and presentations was that a lot of people seem to be very excited about new SGLT-2 inhibitors coming to market!
Professor Clifford Bailey from Ashton University in Birmingham, UK, has been a worldwide expert on these type of emerging medications for years. He was an expert witness for the FDA on Metformin in the past. He took a few minutes at the ADA Conference to help me better understand SGLT-2 drugs.
"Type 2 diabetes is like a river," he said, meaning you can't really cross it in the same place twice because it's always moving and you need to find different points to get across depending on the hour and water conditions.
"With diabetes, we need to find a variety of agents for different stages," Bailey said. "Any new agent can hopefully target aspects of the disease in ways we haven't done yet, and could be used at various stages of the disease progression."
Nothing's been approved yet, but several companies are working on SGLT-2 inhibitors and two have already submitted evaluation information to the FDA (and this new class already has positive feedback in Europe). They seem to be studying SGLT-2s mostly as an add-on drug to be used in conjunction with other therapies:
• Bristol-Myers Squibb reported that its SGLT-2 inhibitor, Dapagliflozin, produced "significant reductions" in blood sugar levels when used during a 48-week period in conjunction with Sitagliptin (brand name Januvia). The study of 447 adult type 2s compared a placebo to a combination of Sitagliptin and Dapagliflozin in patients who were previously not achieving "the desired level of glycemic control." Bristol-Myers has applied for FDA of Dapagliflozin, but in January the agency asked for more data on the drug's risk-benefit profile.
• Janssen Pharmaceuticals, a company of Johnson & Johnson, presented results from five phase 3 clinical studies of its new SGLT-2 drug Canagliflozin, used alone and also in a head-to-head comparison with Sitagliptin. In both cases, Janssen reports that type 2 patients taking Canagliflozin experienced lower A1Cs, greater weight loss, lower blood pressure, and higher HDL cholesterol (the good kind) than patients on Sitagliptin alone. Janssen has submitted Canagliflozin to the FDA for approval as a type 2 therapy.
• Eli Lilly and Boehringer Ingelheim are collaborating on a new SGLT-2 drug called Empagliflozin. Results from a 90-week study showed that using it alone or in combination with Metformin reduced both A1C levels and body weight. The Pharma partners also reported that this Empagliflozin/Metformin combination outperformed the enzyme-inhibitor sitagliptin by Merck & Co. Empagliflozin is currently in a phase 3 clinical trials that will enroll 14,500 people.
While we've been hearing about these SGLT-2 inhibitors for a few years as the "latest and greatest" in novel type 2 treatment, it is also being studied for it's potential value in treating type 1 diabetes, in combination with insulin (!) Animal studies so far have shown that Empagliflozin combined with low-dose insulin is as least as effective as high-dose insulin treatment.
For both types of diabetes, the research on SGLT-2s is in high gear. There's still a long way to go and the researchers must still still demonstrate safety, which is clearly a No. 1 concern. For example, the reason FDA called for more data on Dapagliflozin is that it looks like there may be a risk of elevated rates of bladder and breast cancer (!) found in clinical studies, not to mention concerns about infections and possible liver damage (!).
Bailey in the UK said identifying those risks is "what these late-stage clinical trials are all about."
"Any new class of drugs is always exciting when you're thinking about what they could do, but at the same time, you're exploring why you maybe can't use them," he said. "Everything has its cautions and we're learning what those are, so we can respect them."
Thank you for that, Researcher People who use a lot of science jargon!
I expect we'll hear a lot more about SGLT-2 drugs in the coming weeks and months.