Diabetes drug

Old Diabetes Drug May Help Stave off Osteoarthritis

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Metformin-treated patients fared better than sulfonylurea users

A photo of a spilled prescription bottle of metformin pills.

Metformin may help cut the risk of osteoarthritis (OA) in those with type 2 diabetes, researchers reported.

In a retrospective cohort study of nearly 21,000 adults with diabetes, those who were taking metformin saw a 24% lower risk for developing OA compared with those taking a sulfonylurea (adjusted hazard ratio [aHR] 0.76, 95% CI 0.68-0.85), according to Matthew Baker, MD, MS, of Stanford University in Palo Alto, California, and colleagues.

Metformin-treated patients saw an OA incidence rate of 27.5 events per 1,000 person-years vs 39.6 events per 1,000 person-years for those treated with a sulfonylurea, the group wrote in JAMA Network Openopens in a new tab or window.

The models were adjusted for age, sex, race and ethnicity, geographical region, education, Charlson comorbidity score, and outpatient visit frequency.

Taking this one step further, Baker’s group stratified the analysis according to patients treated with a sulfonylurea who were previously treated with metformin. Here, the risk reduction for OA was not significantly different from current metformin users (aHR 0.92, 95% CI 0.76-1.12). But these patients previously exposed to metformin still had a significantly lower OA risk than those never exposed (aHR 0.71, 95% CI 0.62-0.81).

“One possible hypothesis for this finding is that individuals in the sulfonylurea group with prior exposure to metformin derived a degree of long-lasting protection associated with the metformin exposure,” the researchers explained. These findings fall in line with previous researchopens in a new tab or window that already suggested a protective OA benefit with metformin, Baker’s group pointed out.

“It is possible that metformin use resulted in more weight loss than sulfonylurea use, and the reduction in OA we observed was mediated primarily by weight loss,” the study authors said, but then added that they “believe metformin likely exerts protective associations beyond what can be attributed to weight loss alone.”

This protective benefit didn’t appear to extend to the risk of joint replacement (aHR 1.04, 95% CI 0.60-1.82). The incidence rate of joint replacement for individuals treated with metformin was 1.5 events per 1,000 person-years, compared with 2.1 events per 1,000 person-years for sulfonylurea-treated patients.

This particular finding diverges from another prior studyopens in a new tab or window that had suggested daily metformin was associated with a 30% lower risk for total knee and hip replacement compared with no metformin.

Data for the present study came from claims of patients covered with commercial or Medicare Advantage from the Optum deidentified Clinformatics Data Mart Database from 2003 to 2019. Among the 20,937 individuals included, 58% were male and the average age was 62 years. All individuals were at least age 40 with type 2 diabetes. Those with type 1 diabetes, existing OA, inflammatory arthritis, or joint replacement were excluded.

The researchers acknowledged that they included patients who switched from metformin to sulfonylureas, but not vice versa, potentially creating some bias in the findings. Another limitation to the study was an inability to account for medication adherence in either treatment group.

“Future interventional studies with metformin for the treatment or prevention of OA should be considered,” suggested Baker’s group.

What Is Ozempic Face? Doctors Explain the Side Effect of the Diabetes Drug

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Experts explain that taking medications like Ozempic and Wegovy, for type 2 diabetes and weight loss, can cause an aged appearance in the face

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Medications intended for type 2 diabetes and clinical obesity — like Ozempic, Wegovy and Mounjaro — are trending on social media as drugs for quick weight loss.

However, some have reported the drugs cause an aged appearance, a side effect that is dubbed “Ozempic face.” One of those people is Jennifer Berger, who told The New York Times that she used Mounjaro (tirzepatide) to lose weight following her pregnancy.

Mounjaro, at higher doses, has been proven to be highly effective for weight loss similar to Wegovy.

Berger explained that although using the drug — taken weekly by injection in the thigh, stomach or arm — allowed her to lose 20 lbs. and she loved her results, the 41-year-old said her face started to look very gaunt.

“I remember looking in the mirror, and it was almost like I didn’t even recognize myself,” she told the outlet. “My body looked great, but my face looked exhausted and old.”

man preparing Semaglutide Ozempic injection control blood sugar levels

Dr. Oren Tepper, a New York-based plastic surgeon, explained to the Times that it’s common for weight loss to deflate key areas of the face, which can result in a person looking more aged.

“When it comes to facial aging, fat is typically more friend than foe,” he said. “Weight loss may turn back your biological age, but it tends to turn your facial clock forward.”

Dr. Paul Jarrod Frank, a dermatologist in New York, coined the term “Ozempic face” to describe this side effect, noting that it’s typically people in their 40s or 50s who are concerned about the sagging that occurs as a result of the weight loss in their face.

“I see it every day in my office,” Frank said. “A 50-year-old patient will come in, and suddenly, she’s super-skinny and needs filler, which she never needed before. I look at her and say, ‘How long have you been on Ozempic?’ And I’m right 100 percent of the time. It’s the drug of choice these days for the 1 percent.”

To restore volume in a patient’s face, doctors will often perform noninvasive, but expensive, procedures such as injecting Radiesse and hyaluronic acid-based fillers or Sculptra injections, which stimulates collagen production. Doctors can also restore volume with a face lift or by transferring fat from other body parts to the face.

A Diabetes Drug Has ‘Significantly Reversed Memory Loss’ in Mice With Alzheimer’s

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A drug developed for type 2 diabetes has “significantly reversed memory loss” in mice with Alzheimer’s disease, and researchers now want to test it on humans.

The treatment is exciting for scientists because it works by protecting the brain cells attacked by Alzheimer’s disease in three separate ways, rather than relying on a single approach.

 

And seeing as the drug has already been tested and approved for use in humans, it’s something that could hit the market a lot faster than other experimental treatment options.

The results have only been seen in mice so far, but the drug “holds clear promise of being developed into a new treatment for chronic neurodegenerative disorders such as Alzheimer’s disease,” said senior author Christian Hölscher of Lancaster University in the UK.

“With no new treatments in nearly 15 years, we need to find new ways of tackling Alzheimer’s,” said Doug Brown from UK organisation, Alzheimer’s Society.

“It’s imperative that we explore whether drugs developed to treat other conditions can benefit people with Alzheimer’s and other forms of dementia. This approach to research could make it much quicker to get promising new drugs to the people who need them.”

Previous research had already established a link between type 2 diabetes and Alzheimer’s – type 2 diabetes is a risk factor for Alzheimer’s, and it also appears to make the disease progress more rapidly.

This could be a result of insulin not getting to the cells properly – insulin is a growth factor which is known to protect brain cells, and insulin resistance has been observed in Alzheimer’s disease brains, as well as being the biological mechanism behind type 2 diabetes.

 So researchers have been investigating whether drugs that treat type 2 diabetes might also benefit Alzheimer’s symptoms for a while now.

They’ve seen previous success in humans with an older diabetes drug known as liraglutide. But this is the first ‘triple agonist’ drug that’s been tested.

The drug, which is referred to only as ‘triple receptor agonist’, or TA, in the paper, acts in multiple ways to protect the brain from degeneration, by activating GIP-1, GIP, and glucagon receptors at the same time.

Seeing as growth factor signalling has been shown to be impaired in the brains of Alzheimer’s patients, the idea was that the drug might help re-stimulate damaged brain cells and protect against further damage.

The researchers tested the drug in mice that had been genetically engineered to have Alzheimer’s disease.

They used a maze to measure the animal’s learning and memory formation, and found that the drug “significantly reversed the memory deficit,” the researchers write.

The drug also:

  • enhanced levels of a brain growth factor which protects nerve cell functioning
  • reduced the amount of toxic amyloid plaques in the brain
  • reduced both chronic inflammation and oxidative stress
  • slowed down the rate of nerve cell loss

“These very promising outcomes demonstrate the efficacy of these novel multiple receptor drugs that originally were developed to treat type 2 diabetes but have shown consistent neuro- protective effects in several studies,” said Hölscher.

There’s still a long way to go before it’s clear whether or not this drug will have the same effect in humans, and whether it’s the best option to move forward with.

“Further dose-response tests and direct comparisons with other drugs have to be conducted in order to evaluate if this new [drug] is superior to previous ones,” Hölscher added.

But the fact that this multi-approach drug has shown such promising results so far is incredibly exciting, and is a great way to start 2018.

After all, more than 5 million Americans are already living with Alzheimer’s, and by 2050 that number could be as high as 16 million. So we definitely need new treatment options.

Which Diabetes Drug Is Best?

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No single drug to treat type 2 diabetes stands out from the pack when it comes to reducing the risks of heart disease, stroke or premature death, a new research review finds.

The analysis of hundreds of clinical trials found no evidence that any one diabetes drug, or drug combination, beats out the others.

Researchers said the results bolster current recommendations to first try an older, cheaper drug — metformin (Glumetza,Glucophage) — for most patients with type 2 diabetes.

“There are very few things experts agree on, but this is one of them,” said Dr. Kevin Pantalone, a diabetes specialist at the Cleveland Clinic and a member of the Endocrine Society.

“Metformin, in the absence of contraindications or intolerability, should be the first-line agent to treat patients with type 2 diabetes,” he said.

Metformin can cause upset stomach and diarrhea, so some patients are unable to stick with it day to day, explained Pantalone, who wasn’t involved in the study. And people with kidney disease generally shouldn’t take it, he said.

More than 29 million Americans have diabetes — mostly type 2, according to the U.S. Centers for Disease Control and Prevention.

The disease, which is often linked to obesity, causes blood sugar levels to be chronically high. Over time, that can lead to complications, such as heart disease, stroke, kidney failure and nerve damage, the CDC says.

There are numerous classes of medications that lower blood sugar levels.

What’s been unclear is whether any of those drugs work better than others in warding off diabetes complications and extending people’s lives.

The new analysis found no obvious winners.

But the researchers also cautioned against drawing conclusions: The trials in the review were not specifically designed to see whether any of the medications prolong people’s lives.

Mainly, they looked at “biochemical” effects — like whether the drugs lower blood sugar, explained Suetonia Palmer, the lead researcher on the work.

“So what we know is that currently, there is no good evidence that one drug can improve life expectancy better than another — either when they are used as the only drug for treatment, or when added to metformin,” said Palmer. She’s an associate professor in the Department of Medicine at the University of Otago, in New Zealand.

For the study, Palmer’s team pulled together results from 301 clinical trials testing nine classes of diabetes drugs.

The medications included older standbys such as metformin, insulin, and sulfonylureas such as glipizide (Glucotrol) and glimepiride (Amaryl). Other trials looked at newer, more expensive classes, including thiazolidinediones such as pioglitazone (Actos) and rosiglitazone (Avandia); and DPP inhibitors, such as sitagliptin (Januvia) and saxagliptin (Onglyza).

Many trials tested only a single medication, but over 100 studies used a drug in combination with metformin.

Overall, metformin worked as well, or better than other drugs when it came to reducing blood sugar levels, the review found.

When it came to preventing complications or lengthening people’s lives, no single drug or drug combination stood out.

But the problem, according to Palmer, was a lack of evidence — which is different from proof that all the drugs are equal, she said.

Pantalone agreed. “This [analysis] included many studies that were of short duration,” he said, noting that some ran for only six months.

“I think the important finding was that there was no signal that one therapy may be more harmful than another from a cardiovascular standpoint,” Pantalone said.

That’s important, he explained, because the U.S. Food and Drug Administration has only required diabetes drugs to undergo cardiovascular safety testing since 2008. So older medications never went through that process.

Plus, Pantalone said, there is evidence from recent trials that two newer diabetes drugs can, in fact, curb the risk of death from heart disease or stroke. Those drugs are an injectable medication called liraglutide (Victoza) and an oral medication called empagliflozin (Jardiance).

However, metformin remains the recommended first-line drug. It not only lowers blood sugar, Pantalone said, but also carries a low risk of hypoglycemia (potentially dangerous drops in blood sugar).

If another drug needs to be added, Pantalone said, the decision should be based on a person’s overall health and the side effects of the different medications.

Some drugs, like insulin and sulfonylureas, are more likely to cause hypoglycemia, for instance. Others can cause weight gain, Pantalone said.

Whatever medication is used, he stressed, lifestyle changes for people with type 2 diabetes remain key.

“Lifestyle modification, through diet changes and regular exercise, is a critical component to any treatment regimen,” Pantalone said.

Diabetes Drug to Be Studied in Heart Failure

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Boehringer Ingelheim and Eli Lilly announced on Wednesday that they were planning two separate outcomes trials to test the effect of the diabetes drug empagliflozin (Jardiance) in patients with chronic heart failure.

The trials herald a remarkable shift in emphasis, as there have been repeated concerns that some classes of diabetes drugs might actually worsen or increase the risk of developing heart failure. Only earlier this month the FDA added a new heart failure warning to the labels of the diabetes drugs saxagliptin (Onglyza) and alogliptin (Nesina).

The new hope for empagliflozin is based on the highly positive results of last year’s EMPA-REG OUTCOME trial, which found a significant reduction in cardiovascular events in patients with type 2 diabetes taking the drug, which is an SGLT2 inhibitor. A second paper examining the heart failure outcomes was published in January in theEuropean Heart Journal. The trial investigators reported “consistent reductions” in hospitalization for heart failure and cardiovascular death in patients with heart failure at baseline or who were taking heart failure medications. Patients in the empagliflozin group were also less likely to need loop diuretics.

Heart failure hospitalization or cardiovascular death was reduced by 34% from 8.5% in the placebo group to 5.7% in the empagliflozin group. The authors calculated a number needed to treat of 35 to prevent one heart failure hospitalization or cardiovascular death over 3 years.

The cardiovascular benefit “was observed very early and was sustained throughout the trial,” according to the researchers. “This suggests that the benefit was not driven by an effect on atherosclerosis.” Although the precise mechanism of benefit is unknown, they speculated about several possible mechanisms, including “osmotic diuresis, effects on plasma volume and sodium retention with modulation of the cardio-renal axis, reductions in arterial stiffness and the rate pressure product, indicating diminished left ventricular afterload, reductions in weight and blood pressure without increases in sympathetic nervous activity, reductions in hyperglycemia with concomitant reductions in insulin levels, and reductions in uric acid.”

Boehringer Ingelheim and Lilly said they would conduct two trials in patients with chronic heart failure, one in patients with type 2 diabetes and one without diabetes.

Diabetes and heart failure are urgent and growing problems, perhaps inevitable results of an aging and increasingly obese population. And they are closely related. Sanjay Kaul, MD, of Cedars-Sinai Heart Institute in Los Angeles, pointed out that “diabetes is prevalent in 25% to 40% of patients with heart failure. Diabetes increases the risk of developing heart failure by two- to five-fold. In patients with established heart failure, diabetes is associated with a 60% to 80% increased risk of cardiovascular and all-cause mortality.”

Kaul said that “the heart failure findings in the EMPA-REG OUTCOME trial were clinically meaningful and statistically persuasive. However, they were not systematically evaluated, in part because they were not highly anticipated. Logically these findings need to be replicated in heart failure patients with and without diabetes. Simultaneously, studies need to be conducted to understand the mechanism(s) of benefit. The planned studies, if positive, will expand the portfolio of evidence in favor of the cardioprotective effects of empagliflozin.”

Milton Packer, MD, of Baylor University in Dallas, also supported the studies. “It makes a great deal of sense to study empagliflozin in heart failure, even in those without diabetes. The mechanisms by which the drug may reduce hospitalizations for heart failure in diabetics are not likely to be specific to diabetics.”

“The real question,” Packer wondered, “is what type of heart failure? The best decision here would be to study empagliflozin in patients with heart failure with a PRESERVED ejection fraction. There are reasons to believe that such patients are likely to have been the type that showed particular benefit in the EMPA-REG trial.”

Diabetes drug may slow growth of pancreatic cancer.

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Researchers including those of Indian-origin may have uncovered a novel mechanism behind the ability of the diabetes drug metformin to inhibit the progression of pancreatic cancer.

Researchers found that metformin decreases the inflammation and fibrosis characteristic of the most common form of pancreatic cancer.

The findings indicate that this beneficial effect may be most prevalent in overweight and obese patients.

The study by researchers at Massachusetts General Hospital (MGH) in US focused on pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer.

Half of those diagnosed with this form of pancreatic cancer are overweight or obese, and up to 80 per cent have type 2 diabetes or are insulin resistant.

Diabetic patients taking metformin – a common medication for type 2 diabetes – have a reduced risk of developing pancreatic cancer; and among patients who develop the tumour,    those taking the drug may have a reduced risk of death.

However, previously the mechanism of metformin’s action against pancreatic cancer was unclear, and no potential biomarkers of response to metformin had been reported.

The researchers first found that levels of hyaluronan, a component of the extracellular matrix, were 30 per cent lower in tumour samples from overweight or obese patients who were taking metformin to treat diabetes than in those who did not take the drug.

In an obese animal model of pancreatic cancer, those that received metformin had reduced expression of both hyaluronan  and collagen-1 and fewer activated pancreatic stellate cells    (PSCs).

Studies in cultured cells identified the signalling pathway by which metformin reduces the production of  hyaluronan and collagen-1 by PSCs and also prevents the recruitment of tumour-associated macrophages, which increase  the inflammatory environment.

In obese mouse models, researchers including Rakesh K  Jain and Priya Suboj from MGH found that metformin treatment  reduced levels of tumour-associated macrophages by 60 per cent and reduced expression of genes involved in remodelling the  extracellular matrix of tumour tissue.

The tumours of animals treated with metformin also had reductions in a metastasis-associated change in cellular characteristics called epithelial to mesenchymal transition(EMT) and in the overall level of metastasis.

These tumour-related effects of metformin appear to be independent of the drug’s effects on metabolic pathways involved in glucose metabolism and body weight.

“We found that metformin alleviates desmoplasia – an accumulation of dense connective tissue and tumour-associated immune cells that is a hallmark of pancreatic cancer – by inhibiting the activation of the pancreatic stellate cells  that produce the extracellular matrix and by reprogrammingimmune cells to reduce inflammation,” said Dai Fukumura from MGH.