Diabetes news

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS 2019

The American Association of Clinical Endocrinologists (AACE) 2019 meeting took place in Los Angeles, California, from April 24 to 28. Dr Christian Mende (University of California, San Diego, California) hypothesized that not only sodium-glucose cotransporter (SGLT) inhibitors, but also glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors are likely to confer renoprotection in the long term. This hypothesis is based on improvements in the urinary albumin:  creatinine ratio (UACR) observed in several cardiovascular outcomes trials (CVOTs). Other thought leaders, including Dr Hiddo Heerspink (University of Groningen, Groningen, Netherlands), share this view based on a meta-analysis that suggests that a 25%-30% reduction in albuminuria strongly predicts that a drug will also decrease the risk of progression to end-stage renal disease (ESRD) by a similar percentage.1 In Dr Mende's words, “a 1% reduction in UACR equals a 1% reduction in ESRD over 4 to 5 years, a very worthwhile endeavor”. Pointing to the 34% lower mean UACR conferred with saxagliptin in SAVOR-TIMI,2 the 14% reduction in albuminuria progression found in CARMELINA with linagliptin,3 the 26% reduction in the diagnosis of persistent macroalbuminuria found in LEADER with liraglutide,4 and the 36% reduction in renal complications in SUSTAIN-6 for semaglutide,5 Dr Mende concluded that the DPP-4 inhibitor class reduces albuminuria by 10%-30%, whereas GLP-1 receptor agonists reduce it by 20%-30% in people with type 2 diabetes (T2D) over the time frame of a CVOT (<4 years for the aforementioned trials). The relatively short length of these trials, posited Dr Mende, is the reason why these albuminuria reductions had not yet materialized into reductions in ESRD or estimated glomerular filtration rate (eGFR). Given a longer time frame (~5 years), he believes they would have.

Dr Robert Toto (University of Texas Southwestern, Dallas, Texas) explored potential subgroup effects in the data of the recently reported CREDENCE renal outcomes trial6 for canagliflozin in T2D and chronic kidney disease (CKD). Dr Toto highlighted the impressive, 30% relative risk reduction (RRR; 95% confidence interval [CI] 0.59-0.82) on the primary renal endpoint (ESRD, doubling of serum creatinine, renal or cardiovascular death). Dr Toto also focused specifically on the 32% RRR (95% CI 0.54-0.82) for ESRD; he noted that few CKD trials have shown an effect on this highly important endpoint alone. But perhaps the most interesting conversation arose from Dr Toto's presentation of CREDENCE subgroup data. He explained that although all subgroups consistently and compellingly favored canagliflozin, the strongest shift was seen in those with Stage 3A CKD (eGFR 45-60 mL/min/1.73 m²), although the subgroup with Stage 3b CKD (eGFR 30-45 mL/min/1.73 m²) also saw statistically significant benefit all on its own.

Dr Richard Pratley (Florida Hospital Diabetes Institute, Orlando, Florida) pushed back against the idea of a single glycemic target in older populations, advocating instead for individualized goals: “The evidence we have for optimal HbA1c in older people with diabetes is largely observational. It suggests an HbA1c of approximately 6% to 8% is probably optimal, but we really need to personalize therapy.” Individualization is the explicit asterisk on all HbA1c target recommendations in every guideline and age group; Dr Pratley explained that it is especially important in older patients, who have variable life expectancies, clinical heterogeneity, and functional heterogeneity. Dr Pratley shared a case to illustrate why a one-size-fits-all approach may not be optimal. An 89-year-old former Navy captain had an HbA1c <6.5%, so Dr. Pratley tried to wean him off of his once-weekly GLP-1 receptor agonist. However, when the man saw his blood sugars begin to creep up, he came in “fightin’ mad”, demanding to reinitiate his GLP-1 receptor agonist. Although the “diabetes targets” moniker in the talk implied HbA1c, Dr Pratley made the excellent point that hypoglycemia is particularly dangerous in the elderly, not only due to unawareness, but also because the elderly may have impaired counterregulatory responses, so their brains may be more sensitive to hypoglycemic insults.