A novel combination therapy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) could help restore fertility in women struggling with obesity, polycystic ovary syndrome (PCOS) and type 2 diabetes (T2D), according to a new clinical report published this week.
Early evidence suggests this drug duo may act as a powerful metabolic bridge to natural conception. As a result, it brings fresh hope to patients. This group has long faced fertility challenges linked to metabolic disease.
PCOS affects a significant number of women of reproductive age worldwide. The condition often causes irregular periods, elevated insulin resistance and infertility. When obesity and T2D coexist, metabolic stress on the reproductive system worsens. Clinicians then focus on both metabolic and hormonal solutions.
The study , published in Cureus , details two real-world cases of women with obesity, PCOS and newly diagnosed T2D. Both patients received a combined therapy of a GLP-1RA. Doctors often use this injectable drug to treat diabetes and obesity. They also took an SGLT2i, an oral drug that lowers blood sugar by promoting glucose excretion in urine.
The results were striking: One woman lost 23 % of her body weight. The other achieved a 10.2 % weight reduction. Both women saw regular menstrual cycles return. Crucially, both conceived naturally within seven months without assisted fertility treatments.
Once doctors confirmed the pregnancies, they promptly stopped the medications, following safety practices. Both women delivered healthy babies. Doctors reported no complications.
Weight loss of 5-10 % is traditionally seen as enough to improve ovulation in women with PCOS.In these cases, much larger drops in body weight may have accelerated metabolic shifts. They also improved ovarian function faster than expected.
The proposed mechanism is clear. GLP-1RAs reduce appetite and slow gastric emptying, helping patients lose weight and improve insulin sensitivity. SGLT2is reduces blood glucose via the kidneys and offers complementary metabolic benefits.
Together, they can significantly reduce insulin resistance. Insulin resistance is a key driver of hormonal imbalance in PCOS that interferes with ovulation.
First, weight loss reduces the metabolic stress on reproductive hormones. Then, lowered insulin resistance supports the hypothalamic-pituitary-ovarian axis, improving ovulation and menstrual regularity. Finally, improved glucose control reduces inflammation , another barrier to fertility.
Experts say this therapy could shrink visceral fat (fat around organs), improve lipid profiles, and lower androgen levels that often block ovulation in PCOS. Combined use of these agents has also shown enhanced efficacy in reducing insulin resistance and body weight compared with either agent alone in broader diabetes research.
In related studies, GLP-1RAs have improved menstrual frequency and reduced hyperandrogenism (a hallmark of PCOS), further supporting their potential role in reproductive health.
Despite the promising results, experts caution that these outcomes come from just a few case reports. Larger observational studies or randomised clinical trials will be necessary before this approach becomes standard care.
Additionally, both GLP-1RAs and SGLT2is are not formally approved as fertility treatments. Clinicians stress that they should be discontinued well before planned conception because of limited safety data during pregnancy and ongoing concerns from animal studies.
Practitioners also warn about possible side effects associated with these drugs: GLP-1RAs can cause nausea, vomiting and gastrointestinal discomfort.
SGLT2is may increase the risk of urinary or genital infections, especially in women.
Clear clinical guidelines are still emerging, and researchers are calling for formal protocols on how to time discontinuation before conception and manage patients through early pregnancy.
GLP-1RAs and SGLT2is are widely used in diabetes and obesity treatment under NICE (National Institute for Health and Care Excellence) guidance when first-line therapies are insufficient. While current NICE guidance doesn’t specifically recommend their use for fertility outcomes, this new evidence may prompt future updates or trials within reproductive endocrinology.
Patients with PCOS seeking fertility support should speak openly with their GP or endocrinologist. Treatment decisions must consider individual metabolic profiles, fertility goals, and the latest evidence on benefits and risks.
Researchers emphasise the need for robust controlled trials to confirm these early findings. If results hold in larger studies, a combination of GLP-1RA and SGLT2i therapy could become a useful tool in the fertility toolkit , especially for women where obesity and metabolic disease have blocked natural conception.
Until then, clinicians and patients must weigh the evidence carefully, balancing potential fertility benefits against established clinical guidelines on pregnancy safety.
Sources:
- Banerjee, M., & Dasgupta, S. (2025). Combined glucagon-like peptide-1 receptor agonist (GLP-1RA) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy to restore fertility in patients with obesity, polycystic ovary syndrome, and incident type 2 diabetes. (Cureus)
- Sridharan, K., & Sivaramakrishnan, G. (2025). Expanding therapeutic horizons: glucagon-like peptide-1 receptor agonists and sodium glucose transporter-2 inhibitors in polycystic ovarian syndrome: a comprehensive review including systematic review and network meta-analysis of randomized clinical trials. Diabetology & Metabolic Syndrome, 17(1), 168. (PMC)
