Early Initiation of GLP-1RA/SGLT2 Lowers CV Risk, Increase HbA1C Control

Early initiation of SGLT2 or GLP-1RA in patients with type 2 diabetes for glucose and cardiovascular risk can provide benefits for patients regardless of their history of cardiovascular disease in the past.

The study found that initiation less than 6 months into antidiabetic therapy can have a significant impact on long term HbA1c control and odds of suffering a cardiovascular event.

Sanjoy Paul, professor of clinical epidemiology and biostatistics at the University of Melbourne, was the lead investigator of the study and presented the findings at the American Diabetes Association (ADA) 2019 Scientific Sessions in San Francisco, CA.

After examining more than 20,000 medical records, investigators found that SGLT2 and GLP-1RA was significantly associated with 47% and 23% higher odds for longer term HbA1c control, and 58% and 52% higher odds for at least two of the CV risk factors.

Paul sat down with MD Magazine® at ADA 2019 to provide physician perspective and explain the clinical takeaways from within the study.

MD Mag: What did you find when comparing early and late initiation of GLP-1RA and SGLT2 for cardiometabolic risk factor control?

Paul: When it comes to the pharmacological management of type 2 diabetes, we know there are now novel anti-diabetes therapies like SGLT2 or GLP-1 RA or DPP-4 inhibitors like incretins. Especially as SGLT2 and GLP-1RA are believed to have extra glycemic benefits, a number of clinical trials and epidemiological studies have reported significant benefit in terms of better cardiovascular risk factor control in patients treated with SGLT2 and GLP-1RA and in terms of cardiovascular risk factor control we mean significant reduction in body weight, some association with a better management of systolic blood pressure, and some association with better lipid management. So, then the natural question is in a progressive disease like type 2 diabetes, if we believe that these therapies could be of benefit for holistic cardiovascular as well as glycemic risk factor management then the natural question comes when to place these therapies in the pathway of therapy management in patients with type 2 diabetes.

We know that the first-line therapy well- accepted internationally is metformin and then the guidelines suggest a host of second line as well as third line therapies. Then, at the population level we want to realize the great potential of extra glycemic benefits apart from the glycemic benefit from these new anti-diabetes therapies — to be more specific SGLT2 and GLP-1RA. Then, we have evaluated if early initiation of SGLT2 or GLP-1RA, to be more specific, within six months of the initiation of first anti-diabetes therapy more commonly metformin is beneficial in terms of clinically achieving risk factor control in terms of blood glucose level HbA1c, systolic blood pressure, and lipids and sustain that control over a period of 18 months to 2 years post initiation of such therapy.

Again, we have used about 3,000 people were patients from the United States who were evaluated on the basis of their use on SGLT2 and about 28,000 people with GLP-1RA with significant median follow-up period of time and what we have observed that the people who are getting these therapies as an intensification are receiving at a very high blood glucose level of about 8.6% of HbA1c. About 70% of them, if not more, already have HbA1c above 7.5% and about 50% of them actually have uncontrolled lipids, if not more. Even though the fact is that about 85% of them are already on lipid modifying therapies. What we have observed is that if we initiate SGLT2 early on — within six months — compared to later initiation, then there is a 45 to 46% higher likelihood of reducing HbA1c to a clinically acceptable limit within six months and sustain it over a period of 18 months to 2 years compared to later initiation. In the case of GLP-1RA, the observed benefit is 22 percent higher likelihood of sustaining, maintaining, reducing, and managing the HbA1C level.

In terms of at least two cardiovascular risk factor control, if we initiate these therapies early on then there is a 30 to 34% higher likelihood or odds of reducing or managing at least two cardiovascular risk factors within 6 months and maintain that sustained at over 18 months to 2 years period of time compared to later initiation and this is adjusted for many other confounders, as you can imagine. So, what this clearly suggests is there is a need to further evaluate using electronic medical records and other population level data how exactly these therapies compared to other existing antibody-diabetes therapies are playing in terms of, not only the short-term benefit of reducing the glucose control but as we know, managing diabetes is not just about glucose but also cardiovascular risk factors. How better we are if we place consider such therapies early on in terms of an early holistic management and more efficient proactive management of cardiovascular as well as glycemic risk factor control in in a progressing disease like type 2 diabetes.