One type of chronic diabetes may reduce the risk of dementia, while the other may increase it

Thiazolidinediones (TZDs), akin to pioglitazone, are protecting sulfonylureas that increase the risk of dementia, in keeping with a brand new observational examine in sufferers with type 2 diabetes.

Data from the US Veterans Affairs National Electronic Medical Records confirmed a 22% decrease risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy in contrast with metformin monotherapy. The obvious protecting results of TZDs have been better amongst individuals with obese or weight problems.

“Our findings present further data to assist clinicians make knowledgeable choices [glucose-lowering medications] For sufferers with delicate or average type 2 diabetes and [who] They are at risk of dementia,” Xin Tan and colleagues wrote in an article revealed on-line on October 11. BMJ Open Diabetes Research and Care.

The outcomes, Tang and colleagues say, “considerably add to the literature on results.” [glucose-lowering medications] on dementia with inconsistent earlier findings. Studies with a follow-up of lower than 3 years have principally reported null associations, while longer-term research have usually produced protecting findings. With a imply follow-up time of 6.8 years, we had ample time to detect a remedy distinction.

“Complement [a] Metformin and sulfonylureas or [a] TZD may partially offset its prodementia results. These findings may assist inform drug choice for aged sufferers with T2D at excessive risk of dementia,” they notice.

Randomized trials are wanted to find out trigger and impact

Ivan Koychev, PhD, senior scientific researcher at Oxford University’s Department of Psychiatry, advised the UK’s Science Media Centre: “This is a big, well-conducted real-world knowledge examine that highlights the significance of testing whether or not pharmaceuticals are helpful in stopping dementia.” it’s doable.”

The findings on TZDs, also referred to as glitazones, are according to current literature suggesting safety towards dementia with other prescription drugs for type 2 diabetes not examined in the present examine, akin to newer brokers akin to glucagon-like peptide-1 (GLP). ) -1) agonists and inhibitors of sodium-glucose cotransporter 2 (SGLT2), mentioned Koychev.

“The principal limitation of this examine is that after the first 2-year interval through which the authors have been , the members may have been prescribed one of the other type 2 diabetes medicine (GLP-1 agonists or SGLT2 inhibitors) that reduce the risk of dementia, and due to this fact may instantly type glitazone. [TZD] it is harder to find out the influence,” mentioned Koychev.

And, he famous, the examine design limits the attribution of causality. “It’s additionally essential to notice that folks with type 2 diabetes have the next risk of growing dementia and cognitive impairment, and these medicine are solely prescribed to those sufferers, so all of this knowledge is from this group of sufferers, not the normal inhabitants.”

James Connell, PhD, is Head of Translational Science at Alzheimer’s Research UK. “Although this observational examine discovered that folks with type 2 diabetes who took thiazolidinediones had a decrease risk of dementia than those that used the most typical medicine for type 2 diabetes, it solely reveals an affiliation between the drug and the risk of dementia, not causation. .”

“Double-blind and placebo-controlled scientific trials are wanted to find out whether or not a drug works [TDZ] It might help reduce the risk of dementia in individuals with and with out diabetes. Anyone who has any questions on the remedy they’re receiving ought to converse to their physician,” he advised the UK’s Science Media Centre.

Contraindications of sulfonylureas, metformin versus TZDs

Tang, Mel and Enid Zuckerman College of Public Health, Department of Epidemiology and Biostatistics, University of Arizona, Tucson, and colleagues studied 559,106 VA sufferers with type 2 diabetes who began glucose-lowering drugs between 2001 and 2017. no less than one 12 months. They have been aged over 60 years and didn’t have major dementia. The majority have been white (76.8%) and male (96.9%), two-thirds (63.1%) have been overweight, and the imply A1c was 6.8%.

Overall, 31,125 developed dementia from all causes. The incidence fee was 8.2 instances per 1,000 individuals, starting from 6.2 instances per 1,000 individuals receiving metformin monotherapy to 13.4 instances per 1,000 individuals receiving each sulfonylureas and TZDs.

Compared with metformin monotherapy, the hazard ratio (HR) for all-cause dementia was considerably 1.12 for sulfonylurea monotherapy. An elevated risk was additionally noticed for vascular dementia, with an HR of 1.14.

In distinction, TZD monotherapy was related to a considerably decrease risk of all-cause dementia (HR, 0.78) in addition to Alzheimer’s illness (HR, 0.89) and vascular dementia (HR, 0.43) in contrast with metformin monotherapy. .

Combinations of metformin and TZDs additionally lowered the risk of all-cause dementia, whereas sulfonylurea-containing regimens elevated the risk of all-cause and vascular dementia.

Most of the outcomes didn’t change considerably when the window of drug publicity was prolonged to 2 years.

The impact is extra pronounced in overweight sufferers

The 1-year protecting impact of TZD monotherapy and metformin plus TZD was considerably better amongst members youthful than 75 years and with a physique mass index (BMI) better than 25 kg/m in contrast with metformin alone.two in contrast with individuals older than 75 years and with a standard BMI, respectively.

On the other hand, the elevated risk for dementia with sulfonylureas was additionally elevated amongst these with the next BMI.

This analysis was funded partly by grants from the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Heart, Lung, and Blood Institute. Zhou didn’t disclose additional. Koychev is the principal investigator of the Oxford University-sponsored and Novo Nordisk-sponsored trial testing whether or not the GLP-1 agonist semaglutide reduces the risk of dementia in older adults.

BMJ Open Diab Res Care. 2022;10:e002894. full textual content

Miriam Tucker is a contract journalist primarily based in Washington, DC. He is a daily contributor to Medscape, with other work showing in The Washington Post, NPR’s Shots weblog, and Diabetes Forecast. She is on Twitter: @MiriamETucker.

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