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The Latest in Diabetes Drugs: Less Hypoglycemia, More Weight Loss

By Emma Ryan and Payal Marathe

Research presented at EASD 2017 showcased drugs, both new and old, that improve blood sugar management, weight loss, heart health, and even blood pressure

New research presented at the recent European Association for the Study of Diabetes (EASD) conference showed promising results, including lower A1c, better heart health, weight loss, and less hypoglycemia (low blood sugar). Click to read more about the most notable updates on new therapies:

  • Semaglutide – a once-weekly GLP-1 injection for type 2 diabetes (under FDA review after a very positive Advisory Committee meeting in which four diaTribe Foundation volunteers participated)

  • Bydureon – a once-weekly GLP-1 injection for type 2 diabetes (available now, with a newly-approved, easier way to take it)

  • Add-on pills for type 1 – SGLT “class” Farxiga (available now) and sotagliflozin (in development)

  • Tresiba – a once-daily basal insulin for type 1 and type 2 (available now)

  • Sulfonylureas versus pioglitazone – type 2 diabetes pills (available now)

  • Glimepiride versus ertugliflozin – type 2 diabetes pills (available now and in development, respectively)

The EASD meeting also included discussions of much more than diabetes drug therapies. You can read diaTribe’s coverage of a study showing improved outcomes from CGM use during pregnancy and The diaTribe Foundation’s event on “Solvable Problems in Diabetes.”  

Semaglutide– a once-weekly injection for type 2 diabetes (under FDA review)

Researchers presented new weight loss data on semaglutide, a once-weekly GLP-1 agonist that is currently under FDA review. The SUSTAIN 6 trial showed that people with type 2 diabetes on the lower dose of semaglutide lost more weight – an average of 8 pounds (4% of their body weight) – compared to about 1 pound lost on placebo. People taking the higher dose of semaglutide lost an average of 11 pounds (5% of their body weight) compared to 1.5 pounds on placebo. Additionally, an impressive one in five people on higher-dose semaglutide lost 10% or more of their body weight, compared to about one in 15 people on placebo. Notably, this weight loss was sustained over a two-year period.

Based on previous results showing that semaglutide lowers A1c, Novo Nordisk has submitted the drug to the FDA and EMA for approval. A decision is expected at the end of this year.

Bydureon – a once-weekly GLP-1 injection for type 2 diabetes (available now, with a newly-approved, easier way to take it)

Results from the EXSCEL trial showed that Bydureon, a once-weekly injectable GLP-1 agonist for people with type 2 diabetes, is not any riskier for the heart than placebo (a “nothing” pill). In fact, Bydureon narrowly missed the threshold for showing heart benefits. These positive results follow research announced earlier this year showing that 20% more people taking Bydureon achieved an A1c target of less than 7% than those on placebo.

Both sets of results contribute to evidence showing that the entire group or “class” of GLP-1 agonists reduce A1c and body weight and have neutral (Bydureon) to positive (Victoza) effects on the heart. On a related note, an easy-to-use autoinjector called Bydureon BCise (rhymes with “precise”), featuring easier mixing and injection and a pre-attached needle, has been approved by the FDA – stay tuned for full coverage.

Add-on pills for type 1 – SGLT “class” Farxiga (available now) and  sotagliflozin (in development)

Trial results for two non-insulin drugs that come in pill form offer exciting new options for people with type 1 diabetes to manage blood sugars. inTandem3 looked at sotagliflozin, a once-daily SGLT-1/2 dual inhibitor that has not yet been approved by the FDA. DEPICT 1 studied Farxiga, a once-daily SGLT-2 inhibitor that is approved for treating type 2 diabetes but not type 1. Both studies reported A1c reductions and weight loss – great for the push to approve add-on therapies for type 1. See our previous coverage for more details on this promising new group of add-on therapies for people with type 1.

Tresiba – a once-daily basal insulin for type 1 and type 2 (available now)

New analysis from the DEVOTE trial drove home the significance of severe hypoglycemia, expanding upon previous results showing that basal insulin Tresiba reduced the risk of severe hypoglycemia by 40% relative to basal insulin Lantus.

The analysis of DEVOTE 2 and DEVOTE 3 results showed significant links between daily blood sugar variability and death, suggesting that Tresiba benefits patients by reducing these swings (glycemic variability). This evidence reinforces that drugs that lower the risk of hypoglycemia – and therefore the possibility of hospitalizations and death – are critical in the diabetes treatment toolbox.

Sulfonylureas compared to pioglitazone – type 2 diabetes pills (available now)

The TOSCA.IT study examined the heart safety of pioglitazone, a once-daily pill (TZD), versus sulfonylureas in patients with type 2 diabetes on metformin. Both drugs are generic, low-cost options for additional therapy when metformin isn’t enough, but sulfonylureas have been attracting growing concern about safety. This large heart health outcomes trial compared pioglitazone with three sulfonylureas (glimepiride, glibenclamide, and gliclazide).

  • There was no difference in heart safety between pioglitazone and sulfonylureas, but pioglitazone did result in longer-lasting A1c-lowering and reduced hypoglycemia (low blood sugar).

  • Pioglitazone users had a 90% reduction in severe hypoglycemia – 2% of people on sulfonylureas had an incident of severe hypoglycemia (blood sugar less than 60 mg/dl AND requiring assistance), while less than 0.2% of pioglitazone patients experienced severe hypoglycemia.

  • There was also less than half as much moderate hypoglycemia (blood sugar less than 60 mg/dl, but not requiring assistance) in the pioglitazone group (10%) compared to the sulfonylurea group (32%).

Two other classes of A1c-lowering drugs, SGLT-2 inhibitors and GLP-1 agonists (Jardiance, Invokana, Victoza), have demonstrated heart benefits for people with diabetes. Based on this trial, neither TZD’s nor sulfonylureas showed similar benefits, but sulfonylurea was the clear loser on hypoglycemia. On the other hand, Jardiance, Invokana, and Victoza are not yet generic, meaning they tend to be more expensive. 

Glimepiride compared to ertugliflozin – type 2 diabetes pills (ertugliflozin in development)

The Vertis SU study compared glimepiride (a sulfonylurea) with a more advanced A1c-lowering drug, ertugliflozin (an SGLT-2 inhibitor in development). The trial looked at the A1c-lowering, weight loss, and blood pressure effects of the two drugs in people already taking metformin. After one year of treatment, the researchers found the following results:

  • There was no significant difference in A1c lowering between people taking glimepiride and people taking the higher dose of ertugliflozin (A1c was lowered 0.6% and 0.7%, respectively).

  • People on ertugliflozin lost an average of 7 to 8 pounds, while people on glimepiride gained an average of 2 pounds.

  • There was a significantly higher occurrence of hypoglycemia in the glimepiride group (19%) than on ertugliflozin (3% to 5%).

  • Blood pressure decreased by an average of 2 to 4 mmHg on ertugliflozin, and increased by an average of 1 mmHg in the group taking glimepiride.

Assuming it becomes accessible, this SGLT-2 – instead of a sulfonylurea, which has safety concerns – can offer many benefits for people with type 2 diabetes: a similar effect on A1c (with high dose ertugliflozin), weight loss, blood pressure, and hypoglycemia benefits.

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