Breaking News
February 23, 2019 - Mogrify to accelerate novel IP and cell therapies using $3.7m USD funding
February 23, 2019 - Johns Hopkins study describes cells that may help speed bone repair
February 23, 2019 - Scientists demonstrate influence of food odors on proteostasis
February 23, 2019 - Researchers unlock the secret behind reproduction of fish called ‘Mary’
February 23, 2019 - Acupuncture Could Help Ease Menopausal Symptoms
February 23, 2019 - Researchers use AI to detect early signs of Alzheimer’s
February 23, 2019 - On recovery, vulnerability and ritual: An exhibit in white | News Center
February 23, 2019 - Memory Stored in Unexpected Region of the Brain
February 23, 2019 - Several health experts worldwide gather at EUDONORGAN event
February 23, 2019 - Discovery of potent compound in native California shrub may lead to treatment for Alzheimer’s
February 22, 2019 - Researchers create new map of the brain’s own immune system
February 22, 2019 - ICHE’s reviews on surgical infections, unnecessary urine tests, and nurses’ role in antibiotic stewardship
February 22, 2019 - UK Research and Innovation invests £200 million to create new generation of AI leaders
February 22, 2019 - Takeda collaboration to boost fight against Alzheimer’s and other neurodegenerative diseases
February 22, 2019 - Heavy drinking may change DNA, leading to increased craving for alcohol
February 22, 2019 - U.S. opioid deaths jump fourfold in 20 years; epidemic shifts to Eastern states | News Center
February 22, 2019 - 5 Questions with William Turner on Diversity in Medicine
February 22, 2019 - HHS Finalizes Rule Seeking To Expel Planned Parenthood From Family Planning Program
February 22, 2019 - Researchers uncover biochemical pathway that may help identify drugs to treat Alzheimer’s
February 22, 2019 - Biologist uses new grant to find ways to eliminate schistosomiasis
February 22, 2019 - Bag-mask ventilation to help patients breathe during intubation prevents complications
February 22, 2019 - AbbVie Announces New Drug Application Accepted for Priority Review by FDA for Upadacitinib for Treatment of Moderate to Severe Rheumatoid Arthritis
February 22, 2019 - Nature versus nurture and addiction
February 22, 2019 - New website connects researchers with data experts, resources | News Center
February 22, 2019 - Today’s Concerns About Drug Prices Echo The Past
February 22, 2019 - CT and Doppler equipment have low accuracy in detecting cerebral vasospasm and ischemia
February 22, 2019 - Study finds out similarity in function between healthy retina cell and tumor cell
February 22, 2019 - CWRU awarded NIH grant to identify effective treatments for intimate partner violence
February 22, 2019 - Oncotype DX Not Cost-Effective for Low-Risk Breast Cancer
February 22, 2019 - Scientists discover new type of immune cells that are essential for forming heart valves
February 22, 2019 - Talk About Déjà Vu: Senators Set To Re-Enact Drug Price Hearing Of 60 Years Ago
February 22, 2019 - Genetic defect linked to pediatric liver disease identified
February 22, 2019 - New cellular atlas could provide a deeper insight into blinding diseases
February 22, 2019 - Growing number of cancer survivors, fewer providers point to challenge in meeting care needs
February 22, 2019 - Innovative compound offers a new therapeutic approach to treat multiple sclerosis
February 22, 2019 - $1.5 million grant to develop opioid treatment program for jail detainees
February 22, 2019 - FDA’s new proposed rule would update regulatory requirements for sunscreen products in the U.S
February 22, 2019 - Most Hip, Knee Replacements Last Decades, Study Finds
February 22, 2019 - Wellness problems prevalent among ob-gyn residents
February 22, 2019 - In the Spotlight: “The world is your oyster in geriatrics”
February 22, 2019 - Successful testing of multi-organ “human-on-a-chip” could replace animals as test subjects
February 22, 2019 - Analysis of cervical precancer shows decline in two strains of HPV
February 22, 2019 - Sugary stent eases suturing of blood vessels
February 22, 2019 - From surgery to psychiatry: A medical student reevaluates his motivations
February 22, 2019 - Is New App From Feds Your Answer To Navigating Medicare Coverage? Yes And No
February 22, 2019 - New pacemakers powered by heartbeats could reduce need for surgery
February 22, 2019 - The United States records highest drug overdose death rates
February 22, 2019 - Heart attacks more likely to be fatal in women and rates are rising
February 22, 2019 - Morning walks could be better than drugs at lowering blood pressure
February 22, 2019 - Phase 1 data reinforce safety profile of new drug for treating Duchenne muscular dystrophy
February 22, 2019 - Vitamin D supplementation less effective in the presence of obesity, shows study
February 22, 2019 - Novostia raises CHF 6.5 million to advance its aortic, mitral heart valve to clinical trials
February 22, 2019 - CPRIT awards nearly $20 million to The University of Texas MD Anderson Cancer Center
February 22, 2019 - Sarepta Announces FDA Acceptance of Golodirsen (SRP-4053) New Drug Application for Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 53
February 22, 2019 - An institutional effort to reduce the amount of opioids prescribed following lumbar surgery
February 22, 2019 - Family-history-based models perform better than non-family-history based models
February 22, 2019 - Failure to take statins leads to higher mortality rates | News Center
February 22, 2019 - New study explains why some patients report phantom sensations after limb amputation
February 22, 2019 - First motor-controlled heart valves implanted by Mainz University Medical Center
February 22, 2019 - Novel preclinical model mimics persistent interneuron loss seen in preterm infants
February 22, 2019 - Global health burden of glaucoma has increased, study reveals
February 22, 2019 - A holistic approach key to minimize treatment complexity in patients with interstitial lung disease
February 22, 2019 - 1 in 10 middle-aged Chinese adults are at high risk for heart disease, finds study
February 22, 2019 - More than half a million breast cancer patient’s lives saved by improvements in treatment
February 22, 2019 - Study finds no evidence that tougher policies prevent teenage cannabis use
February 22, 2019 - New blood test detects genetic disorders in fetuses
February 22, 2019 - Lower Self-Perception Observed in Children With Amblyopia
February 22, 2019 - Up to 15 percent of children have sleep apnea, yet 90 percent go undiagnosed
February 22, 2019 - Rare pulmonary defect prompts parents’ nationwide search for answers | News Center
February 22, 2019 - Lesbian and bisexual women at greater risk of being overweight, study finds
February 22, 2019 - UQ research may explain why vitamin D is essential for brain health
February 22, 2019 - Heart Attacks Rising Among Younger Women
February 22, 2019 - How your smartphone is affecting your relationship
February 22, 2019 - Orthopaedic surgeon receives prestigious award, $10 million grant | News Center
February 22, 2019 - New sepsis test could save thousands of lives
February 22, 2019 - Cervical cancer could be eradicated by 2100
February 21, 2019 - Sustained smoking cessation can lower risk of seropositive RA
February 21, 2019 - Thousands with chronic UTIs are not receiving the treatment they need
February 21, 2019 - Are teens getting high on social media? The surprising study seeking the pot-Instagram link
February 21, 2019 - Stanford expands biobank services | News Center
SGLT2 Inhibitors for Diabetes Linked to Increased Risk for Amputation

SGLT2 Inhibitors for Diabetes Linked to Increased Risk for Amputation

image_pdfDownload PDFimage_print

THURSDAY, Nov. 15, 2018 — A specific class of diabetes medication appears to double the risk of losing a leg or foot to amputation, a new study reports.

People on sodium-glucose cotransporter2 (SGLT2) inhibitors were twice as likely to require a lower limb amputation as people taking another type of diabetes medication, Scandinavian researchers found.

Patients also had a doubled risk of diabetic ketoacidosis, a life-threatening complication in which acids called ketones build up in the bloodstream.

“Patients at high risk of amputation, for example those with peripheral artery disease or foot ulcers, might be monitored more closely if SGLT2 inhibitors are used, and the risk of this adverse event may be considered when deciding on which drugs to use,” said lead researcher Dr. Peter Ueda, a postdoctoral researcher with Karolinska University Hospital in Stockholm, Sweden.

SGLT2 inhibitors include dapagliflozin (Farxiga), empagliflozin (Jardiance) and canagliflozin (Invokana and Invokamet).

“The way this class of medications works is if you have higher blood sugars in you, it actually causes an increase in urination because that’s how your body will dispose of the extra sugar,” explained Dr. David Lam. He’s an assistant professor of medicine, endocrinology, diabetes and bone disease at the Icahn School of Medicine at Mount Sinai in New York City.

The U.S. Food and Drug Administration issued a warning in 2017 that two large clinical trials had linked canagliflozin to an increased risk of leg and foot amputations.

However, other clinical trials have revealed no such amputation risk in either dapagliflozin or empagliflozin, said Dr. Kevin Pantalone, an endocrinologist with the Cleveland Clinic.

In this new observational study, 61 percent of patients were using dapagliflozin, 38 percent were on empagliflozin and just 1 percent on canagliflozin.

“They’re reporting an increased risk that hasn’t been observed in prospective, randomized, placebo-controlled trials, and that’s the gold standard,” Pantalone said. “Yes, it’s interesting they find this observation in patients who are on SGLT2 inhibitors, but only 1 percent of the patients were on the drug that is really concerning for harm.”

Ueda agreed that the clinical trial data on record for dapagliflozin or empagliflozin does not jibe with the results.

For this study, Ueda and his colleagues analyzed national health data from Sweden and Denmark for 17,213 patients taking SGLT2 inhibitors and 17,213 patients taking GLP1 receptor agonists between July 2003 and December 2016.

Use of SGLT2 inhibitors was associated with a twofold increased risk of lower limb amputation compared to people on GLP1 receptor agonists. Risk of diabetic ketoacidosis also was doubled.

Researchers tried to control for a large number of other factors that could otherwise explain this association, such as disease history, other medications, and social and economic conditions for the patients. But the study did not prove that these drugs caused amputation risk to rise.

“Although we used a strict study design and accounted for a large number of patient-related variables in our analyses, the results could be affected by unmeasured differences in the characteristics of the patients receiving SGLT2 inhibitors vs. the comparator drug,” Ueda said. “This is always the case with observational studies and the reason why findings from such studies should be considered with caution.”

Pantalone and Lam said one potential way that SGLT2 inhibitors might increase amputation risk is due to the way they work in the body.

Many people who are diabetic have poor circulation in their legs and feet, and these drugs cause people to excrete more urine to lower their blood sugar, the doctors said.

“You could potentially get more dehydrated if your blood sugars are very elevated,” Lam said. “Because of the decrease in blood volume, it’s decreasing overall blood flow and that might be compromising someone who’s already at risk for having poor blood circulation to their lower extremities. It could be making an existing problem worse.”

The conflicting results between this observational study and previous clinical trials means doctors will have to take a patient-by-patient approach, Pantalone and Lam said.

Not every patient taking the drugs needs to stop. “When I have patients come in and they’ve been on it for three years and they’re doing great, they have no history of peripheral vascular disease and no problems, I don’t just take everybody off it,” Pantalone said.

On the other hand, there clearly are patients who might want to avoid SGLT2 inhibitors.

“You just need to think twice,” Lam said. “If this patient has circulatory problems or an active foot ulcer, maybe we should think about a different agent for them.”

“If I have somebody sitting in front of me who already has a history of amputation, this is probably a drug I’m going to avoid,” Pantalone said. “Or if there’s somebody who does have established peripheral vascular disease, maybe this is someone I’m going to avoid prescribing this medication.”

The findings were published Nov. 14 in the journal BMJ.

More information

The U.S. Food and Drug Administration has more about SGLT2 inhibitors.

© 2018 HealthDay. All rights reserved.

Posted: November 2018

Tagged with:

About author

Related Articles