Old Drugs Offer Hope for Treating Diabetes in Those Who Can’t Use Metformin

Old Drugs Offer Hope for Treating Diabetes in Those Who Can’t Use Metformin
Woman uses a blood glucose monitor to check her blood sugar levels. (New Africa/Shutterstock)
George Citroner
2/1/2023
Updated:
3/24/2023

The first drug prescribed to most people with Type 2 diabetes is typically metformin—but for a broad range of reasons, many patients can’t tolerate the drug.

Researchers seeking effective alternatives are looking at a class of older antipsychotic drugs. They found that these drugs can target an enzyme linked to reducing blood sugar.

Their findings are published in the journal Diabetes.
“There is a growing need to find new therapies for Type 2 diabetes,” study lead author John Ussher, a professor in the University of Alberta’s faculty of pharmacy and pharmaceutical sciences, said in a statement.

15 Percent of Patients Can’t Use Metformin

Ussher explained that although metformin is one of the most common therapeutics for Type 2 diabetes, about 15 percent of patients aren’t able to take it and this includes patients at a late stage of the disease.

“When you’re trying to find new therapies or new combination therapies as the disease progresses, it becomes more important to find new drug classes that target new mechanisms so then you have more options to try and lower blood sugar in those individuals,” he said.

Metformin is a first-line choice for most patients with Type 2 diabetes, but there are risks associated with its use. Some people shouldn’t use it at all.

“There is a risk of developing lactic acidosis in taking metformin,” Dr. Jessica Folek, fellowship-trained in endocrine surgery and director of bariatric surgery at Long Island Jewish Forest Hills, part of Northwell Health in New York, told The Epoch Times.

Metformin is contraindicated for people who:
  • Have renal impairment
  • Have congestive heart failure
  • Have a known history of liver disease
  • Are taking carbonic anhydrase inhibitors
  • Are age 65 and older
Gastrointestinal side effects are also common with patients when first taking metformin, including diarrhea, nausea/vomiting, and bloating.
“In most individuals, these side effects improve in the first few days to weeks of starting,” explained Folek. “However, in some, these side effects don’t improve, and they discontinue taking it as a result.”

Older Drugs Are Repurposed to Benefit Patients More Quickly

Drug development is complicated, time-consuming, and expensive.

The process involves clinical trials that test a drug’s safety and efficacy and can take many years to advance from laboratory development to clinical use. Repurposing existing drugs could significantly speed up the process.

While clinical trials are still required, repurposing an existing drug allows scientists to focus specifically on efficacy and safety for the new use. This could make the drug available faster for its new role.

Ussher and his team focused on an enzyme called SCOT, involved in how we make energy from ketones. High activity of SCOT may contribute to Type 2 diabetes.

The researchers discovered an older generation of antipsychotic drugs called diphenylbutylpiperidines (DPBP) that might inhibit SCOT.

These drugs “improve blood sugar control by preventing the muscle from burning ketones as a fuel source,” explained Ussher.

Ussher previously found a DPBP drug called pimozide could be used to treat diabetes, but his team has since expanded its focus to see if more DPBP-class drugs could also work.

“We’ve tested three drugs now, and they all interact with this enzyme,” said Ussher.

Current Alternatives to Metformin

“Alternative medications if [the patient is] unable to take metformin as first-line monotherapy (single medication regimen) include SGLT2 inhibitors,” said Folek.

This drug class includes canagliflozin, dapagliflozin, and empagliflozin (Farxiga, Jardiance, Invokana).

Also available are GLP1 receptor agonists like liraglutide and semaglutide, DPP4 inhibitors, and the gliptins class of medications that includes sitagliptin (Januvia).

Other medications that can be used are sulfonylureas, like glipizide, glyburide, and glimepiride. But Folek emphasized that these aren’t utilized as often as first-line medications because one of their side effects is weight gain.

Patients with significant loss of beta cell function in the pancreas may need to take insulin.

Expert Says There’s a Need for ‘Extreme Caution’

Folek pointed out that researchers need to proceed with extreme caution in repurposing old antipsychotic medications to treat Type 2 diabetes.

Since these drugs are being repurposed to treat diabetes, she suggested that they should be reformulated so they don’t have a psychoactive effect on the brain.

Ussher and his team found these antipsychotic medications also have several serious side effects, some of which are extrapyramidal symptoms. These include involuntary movements such as muscle tremors, contractions, muscle stiffness, facial movements, and restlessness.
Other significant side effects are heart arrhythmias and increased levels of a hormone called prolactin. Symptoms of elevated prolactin include the ceasing of periods in women and the inability to lactate. For both sexes, it can cause infertility, loss of libido, and in men, erectile dysfunction.

“These side effects for the older class of antipsychotic drugs are one of the reasons they are not as widely used as the newer class of medications called ‘atypical antipsychotics,’ which have less of these side effects,” said Folek.

There are other potential side effects, which can adversely affect the quality of life, including lethargy and overall mental slowness.

Type 2 Diabetes Is Preventable

The best ways to prevent Type 2 diabetes are to limit—if not eliminate—consumption of processed foods, “which is hard, as they are everywhere in our society,” said Folek.

The best foods to prevent the condition are those closest to nature.

“Eat whole foods as much as possible and include more vegetables and plant-based foods in our diet,” she explained. “Half of our plate at mealtime should be vegetables and also as colorful as possible to maximize intake of phytonutrients.”

Physical activity is very important as well, and to prevent disease, it is recommended that we include moderate exercise for at least 30 minutes most days of the week for a minimum of 150 minutes per week.

Activities could include gardening, biking, walking, hiking, and other activities.

“Resistance and weight training is also advised as part of your regimen, as it increases your muscles’ sensitivity to insulin,” Folek noted. “The goal is to not get down the path of insulin resistance, which can then lead to Type 2 diabetes.”

George Citroner reports on health and medicine, covering topics that include cancer, infectious diseases, and neurodegenerative conditions. He was awarded the Media Orthopaedic Reporting Excellence (MORE) award in 2020 for a story on osteoporosis risk in men.
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