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Metformin sparks heated discussions among diabetes experts 
  • By Kim Yun-mi
  • Published 2020.05.12 15:21
  • Updated 2020.05.12 15:51
  • comments 0

At an online conference by the Korean Diabetes Association amid the Covid-19 pandemic, diabetes experts focused on discussing whether metformin, early treatment for type-2 diabetic patients, should be used alone as the first-line treatment.

In the “Clinical Diabetes and Therapeutics 1 Session” of the KDA’s conference on Friday, the experts discussed how physicians should treat type-2 diabetic patients in the early stage.

Their opinions varied, ranging from “whether SGLT-2 inhibitors and GLP-1 RA, which have recently proved cardiovascular benefits, were valid as the first-line treatment to replace metformin” to “whether the recent treatment of early combination therapy for a quick control blood sugar was more beneficial than the existing metformin monotherapy.”

New study results and updated treatment guidelines offer the right diabetes treatments. However, doctors often find it difficult to get the same answers in real clinical settings.

The online conference provided an opportunity to hear expert opinions about issues that treatment guidelines cannot address.

Should metformin the only first-line treatment for type-2 diabetes?

Kim Sang-young, a professor at the Endocrinology and Metabolism Department of Chosun University Hospital, said metformin should be the only first-line therapy in type-2 diabetes.

Kim Sang-young, a professor at the Endocrinology and Metabolism Department of Chosun University Hospital, speaks during an online conference by the Korean Diabetes Association on Friday.

Kim said cardiovascular studies of antidiabetic drugs since 2017 have begun to suggest that SGLT-2 inhibitors and GLP-1 RA should be used before metformin to treat diabetes. Last year, the European Society of Cardiology recommended the use of SGLT-2 inhibitors and GLP-1 RA first, rather than metformin, for diabetic patients with cardiovascular diseases or those in the high-risk group, he said.

Although metformin has side effects, a typical gastrointestinal side effect could be controlled through a strategic dose increase or sustained release, Kim noted. “Vitamin B12 deficiency, cited as metformin’s limitations, has yet to be clearly determined at what level complications occur, and monitoring is only recommended in patients with long-term high doses,” he said.

Kim claimed that it was not appropriate to determine the primary therapeutic agent in diabetic patients based solely on cardiovascular outcomes.

As several mechanisms cause diabetes, it is difficult to control blood sugar perfectly with only one drug, he went on to say. Therefore, the “background agent” for diabetic patients should be a drug that is readily available, cheap, and has fewer side effects, he said.

While metformin 1000mg costs 160,600 won ($130.89) annually, an SGLT-2 inhibitor is priced at 312,075 won, and GLP-1 RA, at 1,783,028 won, showing vast differences in prices.

“Metformin has good effects on reducing blood sugars and well-known side effects. It has proven cardiovascular benefits, and it either reduces weight or stays neutral. As it is affordable, too, it can be an excellent background drug,” Kim said.

In contrast, SGLT-2 inhibitors do not have an apparent preventive effect against toxicity caused by long-term use or cardiovascular disease, and they are expensive, he added.

GLP-1 RA is effective, but its injection form makes it difficult to become a first-line treatment, Kim said.

Is early combo therapy better than metformin alone?

Professor Päivi M. Paldánius of Helsinki University gave her keynote presentation, “Is the early combination really better than metformin monotherapy.”

Professor Päivi M. Paldánius of Helsinki University makes a presentation at the KDA’s online conference.

Citing the VERIFY trial, she claimed that early combination therapy was more beneficial than metformin alone when it comes to improving type-2 diabetic patients’ cardiovascular prognosis and maintaining target blood glucose.

The VERIFY study compared the combination of vildagliptin and metformin, a DPP-4 inhibitor, with metformin alone in the initial treatment of newly diagnosed type-2 diabetic patients.

In the five-year trial on 2,001 patients from 34 countries, including Korea, the combo of vildagliptin plus metformin significantly reduced the risk of the first-line and secondary treatment failure, compared to the metformin monotherapy.

“Newly updated guidelines still recommend using metformin in the first-line treatment and correct lifestyles. Instead of introducing guidelines-related inertia, however, we must now accept a modern approach to hyperglycemia management,” Paldánius said, adding that physicians should remove metformin (or any) monotherapy.


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