SAN FRANCISCO -- New data spanning the spectrum of type 1 and 2 diabetes therapies were at the forefront of this year's annual meeting of the American Diabetes Association.
Highlights included a new antibody therapy to delay development in type 1 diabetes, vitamin D failing for diabetes prevention, and cardiovascular outcomes seen with dulaglutide (Trulicity).
The meeting also held more in-depth data on three trials: CREDENCE, CARMELINA, and CAROLINA.
Canagliflozin (Invokana) had a safe cardiovascular and renal profile when used in people with type 2 diabetes and chronic kidney disease, according to a secondary analysis of the CREDENCE trial.
For this cohort of adults with a hemoglobin A1c of 6.5%-12%, eGFR of 30-90 mL/min/1.73 m², and a urine albumin-to-creatinine ratio from 300-5,000 mg/g, canagliflozin given at 100 mg daily had a similar impact on outcomes versus placebo whether patients had a prior cardiovascular event or not:
- Primary prevention of CV death or HF hospitalization: HR 0.74 (95% CI 0.54-1.03)
- Secondary prevention CV death or HF hospitalization: HR 0.66 (95% CI 0.52-0.83)
Renal impact in terms of preventing for end-stage kidney disease, doubling of serum creatinine, or renal or CV death was likewise similar across those using canagliflozin for primary and secondary prevention:
- Primary prevention: HR 0.69 (95% CI 0.54-0.88)
- Secondary prevention: HR 0.70 (95% CI 0.56-0.88)
The similar risk for any adverse events among people on canagliflozin compared with placebo didn't vary according to primary or secondary prevention status either. This included no increased risk for serious adverse events, renal-related adverse events (including acute kidney injury), and fracture. There also wasn't any increased amputation risk, although canagliflozin carries a boxed warning for this.
"The CREDENCE trial of canagliflozin is the first trial in 18 years to show prevention of renal or cardiovascular outcomes in people with type 2 diabetes and at high risk for progressive chronic kidney disease," stated co-investigator Meg Jardine, MBBS, PhD, of the University of New South Wales in Australia, during a press conference. "It's the first study to show for any type 2 diabetes treatment, a cardiovascular benefit in people who had not previously experienced a cardiovascular event -- the primary prevention cohort."
"CREDENCE knocks your socks off, doesn't it?" commented session moderator Robert Eckel, MD, of the University of Colorado Anschutz Medical Campus in Aurora. "Here we have a trial that the composite outcome is really incredibly relevant here."
In a subanalysis of the CARMELINA trial, the DPP-4 inhibitor linagliptin (Tradjenta) demonstrated cardiovascular safety.
Time to first occurrence of cardiovascular death, non-fatal stroke, or non-fatal myocardial infarction didn't differ significantly between people with type 2 diabetes on 5 mg/day of linagliptin compared with those on placebo (HR 1.02, 95% CI 0.89-1.17, P=0.74) over an average follow-up of 2.2 years.
Similarly, time to the cardiovascular endpoint wasn't significantly different among elderly people on linagliptin, nor among those with impaired renal function. Linagliptin also didn't show an increased risk for hospitalization due to heart failure compared with placebo (HR 0.90, 95% CI 0.74-1.08, P=0.26), without variance by age or eGFR status.
In regards to renal risk, time to first occurrence of kidney outcomes wasn't significantly different between linagliptin and placebo during follow-up. Instead, those on linagliptin saw a 14% reduced risk for progression of albuminuria (HR 0.86, 95% CI 0.78-0.95).
"Clinicians out there are using this type of DPP-4 inhibitor in people with kidney disease, and now we can say with confidence ... that it does not increase the cardiovascular [risk]," explained co-investigator Julio Rosenstock, MD, of the University of Texas Southwestern Medical Center, during the press conference. "Since we included these people with advanced kidney disease, we think that we provide additional evidence in the decision making process for selecting medications, especially in this population."
In the CAROLINA cardiovascular outcomes study comparing linagliptin with glimepiride (Amaryl) among people with early type 2 diabetes and elevated cardiovascular risk, those on 5 mg/day of the DPP-4 drug saw no increased risk for the composite cardiovascular outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared with those on 1 to 4 mg/day of the sulfonylurea drug (HR 0.98, 95% CI 0.84-1.14, P=0.76).
All-cause mortality likewise didn't differ between linagliptin and glimepiride during the median 6.3-year follow-up (HR 0.91, 95% CI 0.78-1.06, P=0.23).
Throughout follow-up, there was also no difference between the agents in regards to glycemic control, although there was a slight weight difference, which favored linagliptin. As expected, linagliptin also had a significantly decreased risk for hypoglycemia as compared with glimepiride.
"Other than cost consideration, CAROLINA supports the use of a DPP-4 inhibitor -- in this case linagliptin -- before a sulfonylurea," said co-investigator Rosenstock during the press conference. "We do believe that cardiovascular safety should no longer be a consideration in the decision making process for selecting between either of these two agents."
CREDENCE was supported by Janssen. CARMELINA and CAROLINA were funded by Boehringer Ingelheim and Eli Lilly.
Rosenstock reported relationships with Eli Lilly, Sanofi, Novo Nordisk, Janssen, AstraZeneca, Boehringer Ingelheim, Intarcia, Merck, Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, Genentech, and Lexicon.
Jardine is supported by a Medical Research Future Fund Next Generation Clinical Researchers Program Career Development Fellowship, and reported relationships with Gambro, Baxter, CSL, Amgen, Eli Lilly, Merck, Akebia, Boehringer Ingelheim, Vifor, Janssen, and Roche.
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