Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Prevented Weight Regain in Obese Women with Polycystic Ovary Syndrome Previously Treated with Liraglutide: A Pilot Randomized Study

Ferjan, Simona; Jensterle, Mojca

doi:10.1089/met.2017.0095

Cited by 26 publications

(40 citation statements)

References 28 publications

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“…Other side effects such as edema [21] and bone fractures [22] were also related to the use of pioglitazone. In a previous study, TECOS in adjunct to DMBG prevented weight regain more effectively than DMBG alone in obese women with PCOS previously treated with liraglutide [6]. Another study also showed that TECOS improved beta-cell function and prevented a conversion to impaired glucose tolerance and type 2 diabetes in DMBG-intolerant and obese PCOS patients [23].…”

Section: Discussionmentioning

confidence: 94%

“…Sitagliptin (TECOS) was the first DPP-4 inhibitor approved by the FDA for the treatment of type 2 diabetes. It has been previously observed that TECOS in adjunct to DMBG prevented weight regain more effectively than DMBG alone in obese women with PCOS previously treated with liraglutide [6]. However, the efficacy and potential mechanism of the combination therapy with DMBG and TECOS in PCOS remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Metformin and sitagliptin combination therapy ameliorates polycystic ovary syndrome with insulin resistance through upregulation of lncRNA H19

et al. 2019

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Insulin resistance (IR) is prevalent in women with polycystic ovary syndrome (PCOS). Improvement in insulin sensitivity remains one of the most effective treatment strategies for women with PCOS. This study aims to investigate the efficacy and potential mechanism of the combination therapy with metformin (DMBG) and sitagliptin (TECOS) in PCOS. To address this, insulin was used to treat rat ovarian granulosa cells to establish the cellular PCOS model. Insulin and human chorionic gonadotropin (HCG) were subcutaneously injected into SD rats to establish a rat model of hyperandrogenism with pathogenesis similar to PCOS. Our results showed that co-treatment with TECOS and DMBG attenuated the induced apoptosis and insulin resistance (IR) in PCOS model cells, and improved reproductive hormone disorders, ovarian polycystic changes, and IR of PCOS rats. Mechanistically, upregulation of H19 by H19-expressing lentiviruses enhanced efficacy of combination therapy. Furthermore, co-treatment with TECOS and DMBG induced H19 expression via suppressing the PI3K/AKT-DNMT1 pathway. Collectively, these findings demonstrate that combination treatment with TECOS and DMBG ameliorates PCOS with IR, at least partially, through upregulation of lncRNA H19.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Metformin and sitagliptin combination therapy ameliorates polycystic ovary syndrome with insulin resistance through upregulation of lncRNA H19

et al. 2019

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“…similarly found that sitagliptin prevents weight regain, as compared to metformin alone, in a 12-week prospective open label study in 24 obese women with PCOS previously treated with liraglutide. (47) Thus, a growing body of evidence suggests that sitagliptin selectively reduces VAT. Despite the improvements in VAT and GH secretion, we did not observe an improvement in any of the clinical signs or symptoms experienced by women with PCOS, as reported in a validated PCOS questionnaire.…”

Section: Discussionmentioning

confidence: 99%

Sitagliptin decreases visceral fat and blood glucoses in women with polycystic ovarian syndrome

Devin

Nian

Celedonio

et al. 2019

Preprint

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Context: Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can increase visceral adiposity (VAT) and impair vascular function. GH releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion. Objective: We tested the hypothesis that DPP4 inhibition increases GH and improves glucose levels and vascular function in women with PCOS. Methods: Eighteen women with PCOS participated in a double-blinded, cross-over study. They received sitagliptin 100 mg vs. placebo daily for one month separated by an eight-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT), assessment of vascular function and body composition. Overnight GH secretion was assessed via venous sampling every 10 minutes for 12 hours and analyzed using an automated deconvolution algorithm. Results: During OGTT, sitagliptin increased GLP-1 (p<0.001), early insulin secretion (from mean insulinogenic index 1.9±1.2 (SD) to 3.2± 3.1; p=0.02) and decreased peak glucose (mean -17.2 mg/dL [95% CI -27.7, -6.6]; p<0.01). At one month, sitagliptin decreased VAT (from 1141.9±700.7 to 1055.1±710.1 g; p=0.02) but did not affect vascular function. Sitagliptin increased GH half-life (from 13.9±3.6 to 17.0±6.8 min, N=16; p=0.04) and interpulse interval (from 53.2±20.0 to 77.3±38.2 min, N=16; p<0.05) but did not increase mean overnight GH (p=0.92 vs. placebo). Conclusions: Sitagliptin decreased the maximal glucose response to OGTT and VAT. Sitagliptin did not increase overnight GH but increased GH half-life and the interpulse interval. Precis: Sitagliptin improved body composition and blood glucoses following oral glucose load in women with PCOS. Sitagliptin potentiated GH half-life but did not increase overnight GH levels.

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“…Interestingly, Ferjan et al showed in a pilot randomized study that sitagliptin may prevent weight regain in metformin intolerant obese women with PCOS [162]. The same authors reported that sitagliptin in combination with metformin prevented weight regain more effectively than metformin [163]. Therefore, further studies are warranted to prove a possible therapeutic benefit and advantage of these newer groups of hypoglycemic agents over metformin in the management of PCOS.…”

Section: Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

The Current and Potential Therapeutic Use of Metformin—The Good Old Drug

Drzewoski

Hanefeld

2021

Pharmaceuticals

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Metformin, one of the oldest oral antidiabetic agents and still recommended by almost all current guidelines as the first-line treatment for type 2 diabetes mellitus (T2DM), has become the medication with steadily increasing potential therapeutic indications. A broad spectrum of experimental and clinical studies showed that metformin has a pleiotropic activity and favorable effect in different pathological conditions, including prediabetes, type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM). Moreover, there are numerous studies, meta-analyses and population studies indicating that metformin is safe and well tolerated and may be associated with cardioprotective and nephroprotective effect. Recently, it has also been reported in some studies, but not all, that metformin, besides improvement of glucose homeostasis, may possibly reduce the risk of cancer development, inhibit the incidence of neurodegenerative disease and prolong the lifespan. This paper presents some arguments supporting the initiation of metformin in patients with newly diagnosed T2DM, especially those without cardiovascular risk factors or without established cardiovascular disease or advanced kidney insufficiency at the time of new guidelines favoring new drugs with pleotropic effects complimentary to glucose control. Moreover, it focuses on the potential beneficial effects of metformin in patients with T2DM and coexisting chronic diseases.

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Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Prevented Weight Regain in Obese Women with Polycystic Ovary Syndrome Previously Treated with Liraglutide: A Pilot Randomized Study

Abstract: Sitagliptin in adjunct to metformin prevented weight regain in obese women with PCOS previously treated with liraglutide.

Cited by 26 publications

References 28 publications

Metformin and sitagliptin combination therapy ameliorates polycystic ovary syndrome with insulin resistance through upregulation of lncRNA H19

Metformin and sitagliptin combination therapy ameliorates polycystic ovary syndrome with insulin resistance through upregulation of lncRNA H19

Sitagliptin decreases visceral fat and blood glucoses in women with polycystic ovarian syndrome

The Current and Potential Therapeutic Use of Metformin—The Good Old Drug

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