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Grunberger does not report any relevant financial information.
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Yes. It is not right to put everyone on metformin and wait for it to fail.
George Grunberger
As for SGLT2 inhibitors for first-line therapy in type 2 diabetes, the question should be, why not? What other class of drugs besides insulin can be prescribed and work immediately without the need for titration? SGLT2 inhibitors are insulin independent. There is no risk of hypoglycaemia. There is no risk of weight gain. They work for everyone as long as you have a kidney.
Metformin has been around for decades, costs pennies a day, and is the first choice for type 2 diabetes. However, people forget that a quarter to a third of patients cannot tolerate the full dose of metformin due to gastrointestinal side effects. The dose must also be titrated.
Every other class of antihypertensive drug has its drawbacks. With thiazolidinediones, you measure the complete response in months. GLP-1 receptor agonists must be titrated and adverse gastrointestinal effects may occur. Sulphonylureas have their own problems. With SGLT2 inhibitors, the first pill you swallow works – the response is measured in hours. The only adverse effect to be discussed is the risk of genital mycotic infections, which can be reduced.
Questions like these are of course always hypothetical and unanswerable. There will never be a large-scale, randomized, controlled trial of all the many combinations of drugs for type 2 diabetes to look at long-term, meaningful results. Everything should be patient-centered.
The American Association of Clinical Endocrinology and other groups have stated that if a person with diabetes is the right candidate for SGLT inhibitors, those patients should be started with them immediately, regardless of current or target HbA1c.
As for the cost of getting drugs out of pocket, it shouldn’t be a reason to avoid prescribing this class of drugs. We’re talking about treating patients for the rest of their lives and once they’re generic the cost will come down like metformin. I try to remind people that about 80% of the total societal cost of diabetes is due to long-term complications, hospital stays, revascularization procedures, dialysis, etc. These complications would be prevented if we did the right thing – prescribing a drug like an SGLT2 inhibitor – from the start.
George Grunberger, MD, FACP, MACE, is chairman of the Grunberger Diabetes Institute in Bloomfield Hills, Michigan.
No. Our patients are initially well supplied with metformin.
Daniel Einhorn
In practice, therapy decisions for type 2 diabetes ultimately tend to be “and” rather than “instead of”. The debate is when and not whether SGLT2 inhibitors should be initiated for the right patient.
What’s the rush? When we talk about treating patients with type 2 diabetes rather than heart failure, the argument for bypassing metformin is a storm in a teapot.
There is no data showing that starting metformin as first-line therapy is harmful. For most patients, metformin is drama-free – affordable, well-understood, without bad press, safe, prescribed with confidence, not terrifying to the patient or their family, and potentially beneficial to the heart. VA-IMPACT is a federal government sponsored cardiovascular outcome study for metformin vs. placebo that will be available by 2024. Currently we are relying on older studies where CV benefit was not the primary outcome. Six is reasonably good when it comes to death and hospitalization for heart failure. In every study, the signal for metformin suggests a resume benefit and never hurts. And of course, studies on SGLT2 inhibitors are mainly based on metformin therapy.
Understandably, some doctors find it annoying to base their first diabetes pathogen selection on historical precedents and costs. But why would one suggest bringing the current medical system to its knees by insisting on SGLT2 inhibitors only as the first line of therapy for all patients with type 2 diabetes?
The first prescription of drug telegraph to the patient and family that they have a medical problem serious enough to warrant intervention. This alone can trigger the lifestyle changes that change the course of type 2 diabetes better than any medication. I’ve seen this many times in person. If this HbA1c-based intervention is insufficient, or if an SGLT2 inhibitor independent of HbA1c is valuable for CV or kidney reasons, start the SGLT2 inhibitor after a few months of metformin.
Clinical endocrinologists were ready to beat the data for combination therapy as a need existed. I don’t see any need to be one step ahead of the data here.
Daniel Einhorn, MD, FACE, FACP, is a clinical endocrinologist with Diabetes and Endocrine Associates and medical director of the Scripps Whittier Diabetes Institute in La Jolla, California.
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