Clinical trials on diabetes safety

In 2008, the Food and Drug Administration mandated the pharmaceutical industry to prove cardiovascular safety for all new anti-diabetes medications. As a consequence, we presently have critically useful safety data from clinical trials like LEADER, SUSTAIN, CANVAS, PIONEER 6, DECLARE-TIMI 58, and REWIND.

The FDA has now issued a new draft recommendation to broaden the above requirement by including safety clinical trials for nephropathy, neuropathy, retinopathy, and sleep apnea, in addition to ischemic atherosclerosis. The rationale is that the above non-ASCVD complications can also increase the mortality risk in patients with type 2 diabetes.

Although recommendations have not been specified or finalized, they will change the landscape of anti-diabetes clinical research for the next 15 years. Stay tuned.


Key Revisions of 2020 ADA guidelines

Here you can find the critical modifications in 2020 ADA guidelines. Particular emphasis is placed on pharmacological therapy with GLP-1 agonists or SGLT-2 inhibitors for patients with established cardiovascular disease, heart failure, or chronic kidney disease. Guidelines are published yearly in the month of January.


Testosterone for Women

Women who are diagnosed accurately with hypoactive sexual desire dysfunction (HSDD) and female sexual arousal disorder (FSAD), could benefit from testosterone supplementation. Testosterone therapy appears to be helpful and safe when the dose does not exceed premenopausal physiological levels. For more details, refer to the Global Position Statement published in JCEM in October 2019.


2019 Endocrine Society Guidelines: postmenopausal osteoporosis

The Endocrine Society released its guidelines on postmenopausal osteoporosis in March 2019. The treatment algorithm is primarily based on fracture risk categories. Categories include three essential ingredients; fragility fracture history, T-scores, and FRAX-scores.

Guidelines prefer bisphosphonates, specially alendronate (Fosamax) and zoledronic acid (Reclast), as the first-line therapy for women at high risk of fractures. Denosumab (Prolia) and anabolic hormones (Tymlos and Forteo) can also be used.

Adverse events from osteoporosis therapies ― osteonecrosis of the jaw (ONJ) and atypical femur fractures (AFF) ― have become a public concern in recent years. Although ONJ and AFF are real, the risk of developing fragility fractures from withholding pharmacological therapy far exceeds these potential side effects in high risk and very high-risk women. Providers need to make their patients aware of the benefit vs. harm ratio.


2019 Endocrine Society Guidelines on Metabolic Risk

Endocrine Society recently published new guidelines on metabolic risk. Metabolic risk is characterized similarly to metabolic syndrome (syndrome X) but with the name change to emphasize action rather than description. Presence of three or more of the following entities defines high metabolic risk: high blood pressure, high glucose, high triglycerides, low HDLc, and increased waist circumference.

Although guidelines are similar to those of other national association such as ACC/AHA, ADA, AACE, and NLA; they introduce or emphasize the following elements:

  • Should measure waist circumference routinely.
  • Include A1c in the definition of metabolic risk (vs. fasting glucose only). 
  • Be more aggressive in using statin therapy for primary prevention. 
  • Can add fenofibrate rather than ezetimibe if triglycerides are above 200 mg/dL and HDLc is low.

These guidelines are essential as they further raise awareness of the real cardiovascular and diabetes risk associated with metabolic syndrome, and more importantly encouraging providers to act upon it.

I anticipate elaboration and incorporation of the above critical changes in other national guidelines.  Prevention, always first.


2019 NLA scientific statement: Lp(a) – key points

The various large meta-analysis, Mendelian randomizations, and prospective population-based studies have found the Lipoprotein (a) to be an independent risk factor for atherosclerosis, aortic valve stenosis, and thrombosis. Lp(a) test is considered to be high when its value is >50 mg/dL or >100 nmol/L. These measures correspond to the top 20th percentile of the general population.

Currently, there are no approved specific therapies for Lp(a). The NLA does not recommend the use of Niacin, HRT (hormonal replacement therapy) or Lomitapide (microsomal triglyceride transfer protein inhibitor). Recent trials such as FOURIER and ODYSSEY have shown that addition of PCSK9 inhibitors to Statin therapy can lower Lp(a) by 30%.

However, various guidelines including 2018 AHA/ACC and 2019 NLA scientific statement recommend the use of PCSK9 inhibitors only in the context of uncontrolled LDLc/non-HDLc in patients at high-risk or very-high-risk for ASCVD events.