China
Africa
Explore chapters and articles related to this topic
Allopathic Medicines
Published in Varma H. Rambaran, Nalini K. Singh, Alternative Medicines for Diabetes Management, 2023
Varma H. Rambaran, Nalini K. Singh
In a case study conducted by Charbonnel et al. in 2006, 701 patients with T2DM were screened and randomized to assess the efficacy of sitagliptin with metformin monotherapy. The patients, aged 19–78 years, had mild to moderate hyperglycaemia (mean A1C 8.0%) and were given doses of 1500 mg/day of metformin alongside a placebo or sitagliptin (100 mg once daily) in a 1 : 2 ratio for 24 weeks (Charbonnel et al. 2006, Gallwitz 2007). This combination resulted in sitagliptin treatment showing significant reductions compared with the placebo in A1C (–0.65%), FBG, and 2-hour post-meal glucose in some patients. A significantly greater proportion of the patients achieved an A1C of 7% with sitagliptin (47.0%) when compared to those receiving the placebo (18.3%), and did not experience any adverse effects from this treatment or increased risk of hypoglycaemia. However, some patients experienced body weight loss during the study. The investigating group concluded that combinational therapy, using sitagliptin (at a dosage of 100 mg once daily) alongside metformin, was effective and well-tolerated in patients with T2DM, who had inadequate glycaemic control with metformin alone (Charbonnel et al. 2006). Coincidentally, Janumet, which is presently being marketed by Merck and Co., carries a combination dose of 50/1000 mg (sitagliptin/metformin).
Endocrine Disorders, Contraception, and Hormone Therapy during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Only 16 human pregnancies were reported to the Sitagliptin Registry, and there were no congenital anomalies, but this is purely anecdotal. Animal studies in rabbits and rats given Sitagliptin up to 30 and 20 times the usual human dose during gestation, respectively, had no increased frequency of birth defects. However, the FDA pregnancy risk category is B despite no basis on human experience. The drug crosses the placenta in rodent animal models, but human studies are not published. First trimester exposure to sitagliptin was reported in 30 pregnancies, but only 18 live births resulted (Benhalima et al., 2018). Two of these infants had major birth defects (cleft palate, multicystic dysplastic kidney and hypoplastic adenohypophysis and ectopic neurohypophysis).
Anti-Diabetic Drugs
Published in Awanish Kumar, Ashwini Kumar, Diabetes, 2020
Another ‘incretin’-based therapy includes the DPP-4 inhibitors or the ‘gliptin’ class of drugs, which are oral anti-diabetic medications. DPP-4 is an enzyme present as a transmembrane protein that acts upon the endogenous incretins such as GLP-1 and degrades them. It is due to this enzyme that the half-life of endogenous GLP-1 is almost 5 minutes, which is pharmacologically much less. Thus, inhibition of DPP-4 results in the natural action of endogenous GLP-1 which enhances the insulin secretion. Sitagliptin (Januvia; Merck) was the first drug in this class to be approved by the US FDA in 2006, followed by vildagliptin (Galvus; Novartis) in 2007 [1,15]. Other DPP-4 inhibitors are saxagliptin (Onglyza; AstraZeneca), alogliptin (Nesina; Takeda Pharmaceuticals), linagliptin (Tradjenta; Eli Lilly), trelagliptin (Zafatek; Takeda Pharmaceuticals) and teneligliptin (Tenelia; Daiichi Sankyo). The dosage regimens of these DPP-4 inhibitors are as follows: Sitagliptin (25/50/100 mg once daily), saxagliptin (2.5/5 mg once daily), vildagliptin (50/100 mg per day, not exceeding 100 mg daily), alogliptin (25 mg once daily), linagliptin (5 mg once daily), trelagliptin (100 mg once weekly) and teneligliptin (20 mg once daily). These DPP-4 inhibitors have been used as monotherapy or in combination with metformin, sulphonylureas, TZDs and insulin [16–23]. According to various studies and reports, the major adverse effects associated with DPP-4 inhibitors are pancreatitis, renal problems and even heart failure, which have also been put on the FDA warning list [24]. Therefore, these drugs should be used very cautiously in patients.
Clinical pharmacology of imeglimin for the treatment of type 2 diabetes
Published in Expert Opinion on Pharmacotherapy, 2020
Karl Sebastian Johansson, Andreas Brønden, Filip Krag Knop, Mikkel Bring Christensen
Patients (N = 170, 48% female) with T2D treated inadequately (mean HbA1c 69 mmol/mol (8.5%)) with sitagliptin (a dipeptidyl peptidase 4 (DPP-4) inhibitor) as monotherapy (100 mg OD) were randomized to two arms: Imeglimin 1,500 mg BID or placebo as add-on therapy for 12 weeks. Recruitment was challenged by finding patients treated with sitagliptin monotherapy and eligible subjects, either treatment-naïve (10%) or receiving another antidiabetic monotherapy (90%, mainly metformin), were therefore switched to sitagliptin during a 10-week run-in period. All included patients entered a 2-week continued sitagliptin and added placebo run-in period before baseline measurements and randomization to imeglimin or placebo. Mean age was 57 years and mean BMI 32 kg/m2. Primary outcome was change in HbA1c from baseline [37].
The effect of dipeptidyl peptidase-4 inhibitor and glucagon-like peptide-1 receptor agonist in gestational diabetes mellitus: a systematic review
Published in Gynecological Endocrinology, 2020
Chengcong Chen, Ying Huang, Guoqing Dong, Yongmei Zeng, Ziqiong Zhou
Both insufficient insulin and insulin resistance contribute to the development of GDM [34,35]. It is reported that activation of GLP-1 receptor can ameliorates insulin resistance [36]. Sun et al. reported blood insulin was decreased after treatment, and insulin resistance and β-cell function were also improved [29]. Elkind-Hirsch et al. also demonstrated that insulin resistance, as well as insulin sensitivity were improved in experimental group [30]. It should note that Hummel et al. have investigated if vildagliptin can improve insulin resistance/sensitivity, but the high lost follow-up rate in this trial make the outcomes lack of power [32]. As the two trials that have reported significant results were studied using sitagliptin, whether sitagliptin will be the better choice should be taken into consideration.
TTP399: an investigational liver-selective glucokinase (GK) activator as a potential treatment for type 2 diabetes
Published in Expert Opinion on Investigational Drugs, 2019
The Add Glucokinase Activator to Target A1c (AGATA) trial was a randomized, double-blind, placebo and active-controlled parallel group trial in patients with type 2 diabetes receiving a stable dose of metformin in 21 centers across the United States [49]. The primary endpoint was changed in HbA1c from baseline, and participants (aged 18–75 years, HbA1c ≥ 7.0 and ≤9.5%, BMI 20–45 kg/m2) were randomized to one of the following four treatment groups for a 6-month period: TTP399 (400 mg) once dailyTTP399 (800 mg) once dailySitagliptin 100 mg once dailyPlacebo once daily.