Advancements in diabetes treatment have permeated the area of cardiology and keeping current on these developments is a necessary component of being a cardiologist today. This article throws light on why it is time for cardiologists to take a more proactive approach in managing diabetes, whether borderline or not.

The study

The New England Journal of Medicine published a study comparing semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), to tirzepatide, a medication that acts on both GLP-1a and glucose-dependent insulinotropic polypeptides. [1] GLP-1 receptor agonists promote insulin secretion in hyperglycaemia and inhibit glucagon secretion in euglycaemia and hypoglycaemia.

Additionally, GLP-1 receptor agonists reduce stomach emptying, thus reducing hunger and body weight. Tirzepatide acts as a GLP-1 receptor agonist, but it also increases insulin secretion and lowers glucagon levels in euglycaemia and hypoglycaemia through its glucose-dependent insulinotropic action.

Theoretically, this dual-action offers a number of benefits. Semaglutide 1 mg SQ weekly was compared to tirzepatide 5, 10, or 15 mg SQ weekly in this research. The FDA has not yet authorised tirzepatide.

All three tirzepatide dosages reduced mean haemoglobin A1c (A1c) by 2.01 to 2.3 per cent, compared to semaglutide's 1.86 per cent. Over the course of the 40-week trial, tirzepatide reduced the body weight by 1.9 to 5.5 kg more than semaglutide. However, STEP 2 or the Semaglutide Treatment Effect in People with Obesity trial, employed a semaglutide dosage of 2.4 mg weekly [2], and larger semaglutide doses would very certainly have lowered haemoglobin A1c and body weight more.

Why are cardiologists researching novel diabetes treatments?

Here is the true question. When lovastatin was authorised by the FDA in November 1987, cardiologists were interested in lipid metabolism. And consider where cardiologists are today with regard to cholesterol management via the use of statins, PCSK9 inhibitors, ezetimibe, and bempedoic acid.

The Fourier trial

The lesson learned from LDL control, that "even lower is better," will eventually be applied to A1c management. The Fourier trial showed a 2% absolute risk decrease in cardiovascular events after just three years when high-risk coronary patients used evolocumab to lower their median LDL-C from 92 to 30 mg/dl. [3] 

While existing diabetic studies demonstrate no difference in outcomes for A1c levels more than or less than 7%, these trials utilised insulin to produce the A1c values, and insulin induces hypoglycaemia and has many atherogenic characteristics.

Prediabetes

Additionally, someone diagnosed with "borderline diabetes" has already lost 50% of their insulin-secreting ability. The Diabetes Prevention Program showed that treating individuals with prediabetes, defined as an oral glucose tolerance value of more than 140 mg/dl but less than 200 mg/dl, reduced the risk of developing diabetes by 31%. [4] Hyperglycaemia glycosylates not just haemoglobin, but also the proteins in LDL particles, increasing their inflammatory and atherogenic properties.

In the Early ACS Trial, 32.5 per cent of 879 patients with non-ST segment elevation myocardial infarction (NSTEMI) had known diabetes, 12.2 per cent had undiagnosed diabetes but had fasting glucose values at or above 126 mg/dL or an A1c greater than 6.5 per cent, and 8% had prediabetes defined as a glucose level of 110 to 126 mg/dL. [5] Only 44.4 per cent of participants had normal glucose metabolism.

Prediabetes is a serious condition. It progresses to diabetes and, and along the way, causes cardiac problems. Perhaps it is time for cardiologists to become more knowledgeable, more proactive, and more forceful in their approach to managing diabetes, whether borderline or not.

This article was originally published on October 1, 2021.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.