However, these drugs were less effective at lowering blood sugar levels in older adults than newer drugs called GLP-1s, a category that includes Ozempic (semaglutide) — a finding that surprised researchers, says lead author Peter Hanlon, PhD, clinical senior research fellow at the School of Health and Wellbeing at the University of Glasgow in Scotland. For younger adults, SGLT2 inhibitors were more effective at lowering blood sugar levels compared with GLP-1s.
Although previous large studies didn’t find major differences in how all these medications work based on age, this meta-analysis suggests there may be some variation, says Neda Rasouli, MD, professor of medicine and pharmacy and director of the CU Diabetes and Endocrinology Clinical Trial Program at the University of Colorado School of Medicine in Anschutz. Dr. Rasouli was not involved in this meta-analysis.
“Younger people seemed to respond better to SGLT2 inhibitors for lowering blood sugar compared with older adults, while GLP-1s appeared to lower A1C [a measure of blood sugar levels] more effectively in older individuals,” Rasouli says.
“When it comes to heart protection, SGLT2 inhibitors reduced major adverse cardiovascular events more in older adults, whereas GLP-1s showed a bigger impact in younger people.”
Meta-Analysis Included Data from Over 600 Studies
For the analysis, researchers aimed to find out whether age or sex made a difference in the effectiveness of different type 2 diabetes medications. Scientists analyzed data from 601 randomized clinical trials that included over 395,000 people with diabetes.
There were three types of diabetes medications included:
Available SGLT2 inhibitors include:
- Brenzavvy (bexaglifozin)
- Invokana (canagliflozin)
- Farxiga (dapagliflozin)
- Jardiance (empagliflozin)
- Steglartro (ertugliflozin)
Available GLP-1 medications include:
- Ozempic, Rybelsus (semaglutide)
- Victoza (liraglutide)
- Mounjaro (Tirzepatide)
- Trulicity (dulaglutide)
- Byetta (exenatide)
DPP4 inhibitors include:
- Januvia (sitagliptin)
- Zituvio (sitagliptin)
- Onglyza (saxagliptin)
- Tradjenta (linagliptin)
- Nesina (alogliptin)
The meta-analysis revealed a few key findings, says Susan Spratt, MD, professor of medicine and endocrinologist at Duke Health in Durham, North Carolina, who was not involved in the research:
- The findings confirmed that SGLT2 inhibitors and GLP-1s lower blood sugar and reduce the risk for major adverse cardiac events. DPP4 medications have no impact on heart disease risk.
- DPP4 medications are less effective in lowering A1C levels compared with the other two drug classes.
- There was no difference between the drugs’ effect on blood sugar levels between men and women.
- GLP-1s were more effective in reducing heart attack and stroke risk in younger adults.
- There was no increased risk of side effects in older people.
“The findings suggest that age should not be a barrier to treatment with SGLT2 inhibitors. [Older adults] are likely to benefit from reduced cardiovascular risk,” says Dr. Hanlon.
It also suggests that for SGLT2 inhibitors and GLP-1s, reduction of blood sugar levels may not be the best way to judge how effectively these medications are preventing heart attack and stroke, he says.
GLP-1 Drugs: The Growing Attention Is ‘Well Deserved’
“The GLP-1 agonist medications are popular because they have a lot of benefits, including weight loss, very strong A1C lowering potential, and reductions in major cardiac events such as heart attack and stroke,” says Dr. Spratt.
The weight loss often comes with additional benefits including reductions in sleep apnea and musculoskeletal pain, she adds.
“However, we do need to remember that the SGLT2 inhibitors reduce heart failure risk, improve kidney outcomes, slow progression to dialysis and renal decline, and also lower the risk for major adverse cardiac events like heart attack and stroke,” says Spratt.
The main difference between GLP-1s and SGLT2 inhibitors is their effects on weight loss, says Rasouli.
“SGLT2 inhibitors lead to modest weight loss of around 5 percent, whereas GLP-1s typically result in more significant weight loss, often exceeding 10 percent. Additionally, GLP-1s are generally more effective at lowering A1C compared to SGLT2 inhibitors,” she says.
“The growing attention around GLP-1s is well deserved, as they represent a breakthrough in achieving effective weight loss with a relatively good safety profile. Their added benefits of heart and kidney protection make them even more valuable,” says Rasouli.
Work With Your Doctor to Find the Right Diabetes Medication for You
People should work with their healthcare provider to choose the type 2 diabetes medication that’s right for them, says Spratt.
“Choosing a medication will depend on whether the patient may benefit more by reducing blood sugar levels versus reducing heart disease risk,” she says.
Rasouli agrees that the findings may help guide the selection of the right medication for different age groups. “Precision medicine, or the individualization of care, is the future of healthcare,” she says.
