Treatment failure was prominent among adults with type 2 diabetes (T2D) that initiated treatment of sodium-glucose cotransporter 2 inhibitors (SGLT2is), according to a study in Diabetes & Metabolic Syndrome: Clinical Research & Reviews.1 Highlighting the need for a more optimized approach to SGLT2i treatment, researchers also uncovered a significant clinical and economic burden among this population.
“SGLT2is prevent the reabsorption of glucose into the bloodstream, thereby reducing blood glucose levels,” wrote the authors of the study. “The effects of SGLT2i on glycemic control and reductions in cardiovascular events, chronic kidney disease progressions, and mortality among adults with T2D have been demonstrated in both clinical trials and real-world studies.”
Amid the rise of SGLT2i treatment among patients with T2D, extensive research has been conducted highlighting the benefits of this drug class. However, the glucose-regulating medication has been well-documented as having common adverse effects, which may lead to treatment discontinuation or a decrease in treatment effectiveness.
Frequently reported adverse events regarding SGLT2i treatment typically include urinary tract infections, increased urination, nausea, and constipation. However, this drug class can also lead to more complex events, such as diabetic ketoacidosis, genital mycotic infections, urosepsis, and pyelonephritis. Furthermore, treatment has even been reported as leading to more physical complications such as limb amputation and bone fractures.2
Despite their reported efficacy, glucose-regulating medications have been well-documented as having common adverse effects, often leading to treatment failures. | image credit: wladimir1804 / stock.adobe.com
READ MORE: Weekly GLP-1s Significantly Reduce Cardiovascular Risks
Nonetheless, the use of SGLT2is—similar to the rise in glucagon-like peptide-1 use3—has been reported in-depth and is owed to these medications’ metabolic, cardio-, and nephro-protective roles.4 With 4 FDA-approved SGLT2is (anagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) demonstrating significant efficacy,2 researchers are now looking to address the lack of research regarding patients with T2D’s susceptibility to SGLT2i treatment failure.
“Understanding risk factors for treatment failure and treatment patterns after failure is crucial for improving adherence to the guidelines in clinical practice,” the authors continued.1 “Therefore, the current study also evaluated the risk factors of treatment failure with SGLT2i, as well as treatment patterns and clinical and economic burden among adults who failed SGLT2i.”
Using administrative claims data spanning across millions of US patients, researchers conducted an observational cohort study featuring adults with T2D that started SGLT2i treatment from January 1, 2016, to April 30, 2024. Bexagliflozin, anagliflozin, dapagliflozin, empagliflozin, and ertugliflozin were the SGLT2is included.
Researchers’ primary outcome was treatment failure, defined as discontinuation of the SGLT2i, adding or switching medications, or uncontrolled glycated hemoglobin (HbA1c) without taking action. To further characterize the patient population, investigators also recorded participants’ risk factors, treatment patterns, and clinical and economic burden.
The final analysis featured a total of 237,295 adult patients (mean age, 58.8 years; 44% women; 43.1% white) with T2D. Highlighting significantly poor adherence among the population, 77.3% of the cohort experienced treatment failure for SGLT2is, with the median time to failure being just over 9 months. For the 3 types of treatment failure defined in the study, 39.3% discontinued, 32.3% added on or switched medications, and 5.8% had uncontrolled HbA1c and did not take action.1
Furthermore, those who had failed treatment also experienced higher rates of diabetes complications, leading to more emergency room visits, hospitalizations, and an increase in associated health care costs and use.
They also identified a slew of risk factors that led to treatment failure, such as patients over 74 years old, women, Black participants, and those residing in the southern part of the US. Comorbidities like hypertension, hyperlipidemia, depression, and anxiety, as well as neuropathy and tobacco smoking, were also associated risk factors.
Among the various approaches researchers uncovered to correct treatment failure, they suggested a more careful evaluation of at-risk patients’ risks and benefits of taking SGLT2is before being prescribed them. They also mentioned a proactive management of adverse drug events to prevent discontinuation and prescribing combination therapies of SGLT2i and other glucose-lowering medications.
“This observational cohort study demonstrated high rates of treatment failure, including discontinuation, add-on/switching, and uncontrolled HbA1c without action,” concluded the authors.1 “Treatment failure is associated with increased utilization of other glucose-lowering medications following treatment failure with SGLT2i, particularly GLP-1 receptor agonists, and increased clinical and economic burden. These findings unfold substantial unmet needs among adults with T2D who initiated SGLT2i.”
READ MORE: Diabetes Resource Center
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