SGLT2 inhibitors preferred for adults with type 2 diabetes and heart failure
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Key takeaways:
- SGLT2 inhibitors are the preferred for treating comorbid type 2 diabetes and HF, according to speakers.
- Prescribers should avoid two DPP-IV inhibitors and thiazolidinediones for this group due to HF risks.
HOUSTON — SGLT2 inhibitors should be the first choice of therapy for adults with type 2 diabetes and heart failure, according to two speakers at the Association of Diabetes Care and Education Specialists annual meeting.
Christie Schumacher, PharmD, BCPS, BCACP, BCCP, BC-ADM, CDCES, FCCP, professor of pharmacy practice and director of the PGY2 Ambulatory Care Pharmacy Residency Program at Midwestern University College of Pharmacy, Downers Grove Campus, and clinical pharmacist at Advocate Medical Group in Chicago; and Dejan Landup, PharmD, HF-Cert, clinical pharmacy specialist in heart failure (HF), cardiology and chronic disease management at Advocate Medical Group – Heart Failure Clinic in Chicago, discussed how providers should manage comorbid type 2 diabetes and chronic HF. The presenters advised attendees to prescribe drugs that have established cardiovasscular (CV) safety and benefit.
“For patients with diabetes and HF, SGLT2 inhibitors are preferred, unless there is a contraindication or intolerance present,” Landup said during the presentation. “If [there is a contraindication], you can consider using a GLP-1 receptor agonist with proven CV benefit. Metformin can still be used in our patients with mild to moderate kidney impairment as long as the person with diabetes and HF is hemodynamically stable. It is important to monitor kidney function to ensure adequate perfusion if HF symptoms are worsening. Metformin should be discontinued if the estimated glomerular filtration rate declines to less than 30 mL/min/1.73 m2.”
Diabetes and HF commonly coexist, with up to 22% of people with diabetes also having HF, Landup said. People with diabetes have a 2- to-4-times higher risk for HF compared with those without diabetes, and the coexistence of HF and diabetes is associated with worse outcomes compared with HF alone.
“With the increase in prevalence and aging population, more and more people will have both diabetes and HF, requiring us to be familiar with both disease states in order to take care of our patients and improve outcomes,” Landup said.
SGLT2 inhibitors reduce HF hospitalization risk
Schumacher reviewed CV outcome trials for several drug classes. The first class, DPP-IV inhibitors, are not recommended first-line for use by people with type 2 diabetes and HF, and if a DPP-IV inhibitor is selected, preference should be given to sitagliptin or linagliptin. In a post-hoc analysis of the EXAMINE trial, adults with no history of HF who used the DPP-IV inhibitor alogliptin had an increased risk for hospital admission for HF compared with those using placebo (HR = 1.76; 95% CI, 1.07-2.9). Trial data led the FDA to issue a warning about an increased risk for HF for people with heart or kidney disease using alogliptin or saxagliptin (Onglyza, AstraZeneca) in 2016.
Schumacher said no difference in risk for HF hospitalization was found with GLP-1 use compared with placebo in six CV outcome trials; however, GLP-1 receptor agonists should not be ruled out as a possible therapy for people with type 2 diabetes and HF.
“These trials were only powered to detect a difference in three-point major adverse CV events,” Schumacher said during the presentation. “The fact that they didn’t decrease HF hospitalizations doesn’t mean they don’t — it just means we need more data and more trials. If a person is on a GLP-1 receptor agonist for weight management, continuous re-evaluation of baseline dry weight for HF monitoring should be considered, since we know GLP-1 receptor agonists can lead to considerable weight loss.”
SGLT2 inhibitors have the most benefits in CV outcome trials. Data from trials of five SGLT2 inhibitors revealed adults who took any of the five had a lower risk for hospitalization for HF compared with placebo. The data make SGLT2 inhibitors first-line therapy for HF, according to Landup.
“More specifically, [SGLT2 inhibitors] are indicated in all people with HF with reduced ejection fraction, barring any contraindications,” Landup said. “They should also be considered with mildly reduced or preserved ejection fraction.”
Landup said dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) are the only SGLT2 inhibitors currently FDA-approved to treat HF. He said initial doses for both agents should be 10 mg daily, which is also the target dose. Adults should not receive dapagliflozin if they have an estimated glomerular filtration rate of less than 25 mL/min/1.73 m2 or empagliflozin if they have an estimated glomerular filtration rate of less than 20 mL/min/1.73 m2. Both agents should not be used in people on dialysis until more data is available in this population.
Metformin may also be safe for adults with type 2 diabetes and HF. Schumacher said observational studies have shown people with HF taking metformin have a lower risk for mortality compared with those not taking metformin. However, Schumacher added that adults should not remain on metformin if they are having a HF exacerbation and are hemodynamically unstable or if they have severe kidney insufficiency with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m2.
If patients are unable to take an SGLT2 inhibitor, GLP-1 receptor agonist or metformin, Schumacher said, a sulfonylurea could be prescribed. Data from the CAROLINA trial showed adults using the sulfonylurea glimepiride had no difference in risk for HF hospitalization compared with those using the DPP-IV inhibitor linagliptin (Tradjenta, Boehringer Ingelheim/Eli Lilly).
“If you’re worried about sulfonylureas for HF, as of right now we don’t have any data that shows they are harmful,” Schumacher said. “They are safe, so if cost is an issue, feel free to use one.”
Schumacher said providers should avoid prescribing thiazolidinediones for people with symptomatic HF. The agents may be considered with caution for someone with class I or class II HF according to New York Heart Association functional classification system, but careful monitoring of fluid retention, HF symptoms and daily weights must be performed.
Landup said diabetes care and education specialists play an important role in the management of HF for people with type 2 diabetes. He said providers should monitor the weight of their patients to identify early signs of fluid overload and potential decompensation; encourage them to lower their sodium consumption, quit smoking and reduce their alcohol intake; and monitor their medication use to ensure that appropriate, guideline recommended medications are being utilized while potentially harmful medications are being avoided.
Reference:
Rosenstock J, et al. JAMA. 2019;doi:10.1001/jama.2019.13772.
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Schumacher C, et al. D03. Presented at: ADCES23; Aug. 4-7, 2023; Houston.
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