ADA 2019: Day 4 and 5 Highlights
By Jeemin Kwon, Emma Ryan, Karena Yan, and Ann Carracher
Big focus on heart health outcome trials with PIONEER 6 and CAROLINA in the spotlight; plus promising CGM data in adolescents with type 1 diabetes
The American Diabetes Association (ADA) 79th Scientific Sessions ended on a high note with a full session on PIONEER trials examining oral version of Ozempic (semaglutide). The major theme of these two days was heart health in type 2 diabetes, an area of growing emphasis in diabetes care. What a terrific ADA – stay tuned for continued coverage of the most relevant news!
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We were highly anticipating the full PIONEER 6 results following the release of initial results that showed a 21% risk reduction of heart attack, stroke, and heart-related death. The exhibition hall was packed this morning as results came out! This study compared an oral version of Ozempic (semaglutide), a GLP-1 agonist, against placebo (a “nothing” pill).
It was a very exciting set of presenations – in a population of people with type 2 diabetes and heart disease or risk factors for heart disease, compared to placebo, oral Ozempic:
Reduced risk of heart-related death by 51%
Did not have a meaningful difference in heart attacks
Did not have a meaningful difference in strokes
Reduced A1C by 1.0% from a starting A1C of 8.2%
Reduced weight by about 9 lbs (4.2 kg) from a starting weight of 200 lbs (91 kg) – this is nearly 5% of body weight lost, which is very meaningful
Overall, PIONEER 6 was exciting and further paves the way for the first oral GLP-1 pill to become available for people with diabetes. Presenters were hopeful that taking a pill rather than injecting may remove barriers to use in many. Notalby, oral Ozempic has some fasting requirements – people have to take oral Ozempic on an empty stomach and then wait 30 minutes before eating – and we will see how people with diabetes feel about this when they get closer to approval and launch! For some, it may well be a meaningful hurdle while others will probably sail by this.
Oral Ozempic is currently under review by the FDA and other regulatory agencies. See here for the session slides from the notable Dr. John Buse at UNC, and here for the article published in the New England Journal of Medicine.
The CITY trial tested whether the Dexcom G5 continuous glucose monitor (CGM) could improve outcomes in adolescents (14-25 years) with type 1 diabetes. Compared to BGM, CGM resulted in a 0.4% greater reduction in A1C after six months – impressive given that meeting A1C goals is particularly difficult in this age group. (The average starting A1C was 8.9%.) Those on CGM also experienced 1.4 hours per day more in-range (70-180 mg/dl), slightly less time spent above 180 mg/dl (58% vs. 54% of the day), and less time spent below 70 mg/dl (3.2% vs. 2.2%). These benefits may not seem like a lot, but it’s an hour less time high a day, and 15 minutes less time low a day.
While these results are exciting, Dr. Lori Laffel of the Joslin Diabetes Center emphasized that time spent above 180 mg/dl still comprised over half the day, indicating that more work needs to be done. Encouragingly, good news came from the user reports, which detailed more satisfaction with CGM than BGM and greater perceived benefits of CGM, to name a few. We’re also happy to see that there were no differences in diabetes distress or sleep quality between the CGM and BGM groups – a concern due to CGM alarms.
Participants from both groups are currently being followed for an additional six months using the Dexcom G6. This is such exciting research and we’re thrilled at these outcomes. No matter what your age, if you take insulin for meals and are not on CGM, ask your healthcare provider about it and mention this study!
Previous studies have suggested that a type of medication called sulfonylureas, particularly Orinase (tolbutamide), may be unsafe for the heart. The FDA currently has a product-label warning for heart-related death for all sulfonylureas.
New CAROLINA study results, however, demonstrated that the DPP-4 inhibitor Tradjenta (linagliptin) and the sulfonylurea glimepiride are equally safe for the heart in people with type 2 diabetes. The CAROLINA trial looked specifically at non-fatal heart attacks, non-fatal strokes, and heart-related death. Since we have evidence that Tradjenta is no more dangerous than placebo (a “nothing” pill), there’s reason to believe that glimepiride also poses no heart safety risk – though we don’t know if this applies to other sulfonylureas like glipizide, gliclazide, and glibenclamide.
Interestingly, although sulfonylureas are generally associated with weight gain, the trial also showed no difference between Tradjenta and glimepiride on changes in weight. Participants lost an average of about 1-3 pounds in both groups – because people were really “looked after” in the trials, it’s unlikely that this weight loss would happen with glimepiride in the real world. There were also no significant differences in A1C reduction; both groups experienced an initial drop in A1C that creeped back up to the starting level of 7.1%.
However, sulfonylureas are known to carry a greater risk of hypoglycemia than other type 2 diabetes medications. CAROLINA confirmed increased hypoglycemia with glimepiride, showing a 77% increased risk of hypoglycemia overall; 38% of those on glimepiride experienced hypoglycemia, compared to 11% of those on Tradjenta. Looking more closely, glimepiride had an 85% increased risk of severe hypoglycemia (low blood sugar requiring assistance from a third party) and a 93% increased risk of hospitalization for hypoglycemia. This alone is reason to avoid glimepiride if at all possible. If not, we encourage people to check blood glucose levels as frequently as possible.
Though Tradjenta clearly has the upper hand on hypoglycemia, those who are on glimepiride due to its lower cost can be more assured about heart safety.
21-Year Follow Up of STENO-2 Participants Shows 69% Reduction in Stroke and Additional 8 Years of Life Expectancy
STENO-2 followed people with type 2 diabetes for over two decades to compare outcomes of receiving multifactorial interventions or standard of care. Multifactorial interventions were simultaneous glucose, blood pressure, and lipid lowering over a period of eight years.
Impressively, those receiving the more intensive care had a 69% reduced risk for stroke; 26% in the standard of care group had a stroke, compared to 11% in the intensive care group. The intensive care resulted in an extra eight years of life expectancy.
Though a relatively small trial (160 participants), the long-term and consistently compelling results provide clinical and economic reasons for meeting glucose, blood pressure, and lipids. Dr. Peter Gæde of the Steno Diabetes Center noted that while the intervention is costly in the short-term, it is a very smart investment due to the powerful data on the prevention of complications.
You can find ADA 2019 highlights from days 1-3 below: