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Approach to women with recurrent first-trimester abortions: Need of the hour
Published in Minakshi Rohilla, Recurrent Pregnancy Loss and Adverse Natal Outcomes, 2020
Women on SGLT1 (sodium glucose transporter 1) inhibitors like sotagliflozin for treatment of diabetes should be advised against their use in pregnancy. SGLT1 is expressed in the endometrium and controls glycogen accumulation essential for histiotrophic nutrition in pregnancy. Relative SGLT1 deficiency in the human endometrium at implantation may predispose for early pregnancy failure and obstetric complications, including fetal growth restriction [35].
Anti-Diabetic Drugs
Published in Awanish Kumar, Ashwini Kumar, Diabetes, 2020
Another most recent addition to the list of oral anti-diabetic medicines is a class of drugs known as sodium-glucose co-transporter-2 inhibitors (SGLT-2 inhibitors or the ‘gliflozin’ drug class). These drugs inhibit a member SGLT-2 from a class of cell surface receptors found in the gastrointestinal tract and kidneys. This receptor is responsible for the passive transport of glucose and other monosaccharides. SGLT-2 receptors are primarily found in proximal renal tubules and are highly responsible for renal glucose reabsorption. It was also reported that the expression of SGLT-2 is significantly increased in diabetic patients. Thus, inhibiting these receptors would enhance renal glucose clearance by blocking glucose reabsorption, which raises the plasma glucose concentration. Canagliflozin (Invokana) was the first SGLT-2 inhibitor approved for use [1,4]. It is also the only drug in this class that inhibits SGLT-1 receptors primarily present in the small intestine. Other drugs in this class include dapagliflozin (Forxiga), tofogliflozin (Deberza), empagliflozin (Jardiance), ipragliflozin (Suglat), luseogliflozin (Lusefi) and ertugliflozin (Steglatro). Invokana exists as a 300 mg tablet taken once daily; Forxiga exists as 5 mg and 10 mg tablets and the recommended dose is no more than 10 mg taken once daily; Jardiance comes as 10 mg and 25 mg pills taken once daily; Suglat comes in 25 mg and 50 mg tablets with the maximum dose not exceeding 100 mg per day; Lucefi exists in 2.5 mg and 5 mg pill formulations taken once daily; Steglatro, the latest addition to the class, is available in 5 mg and 15 mg formulations [25–31]. Regarding safety concerns and adverse events, SGLT-2 inhibitors have been shown to be associated with an increased risk of leg and foot amputation, diabetic ketoacidosis, urinary tract yeast infection, vaginal and penile yeast infection, bone fracture (by decreasing bone mineral density) and renal impairment [25–37]. These medications, therefore, should be very cautiously prescribed, taking into account the risk-to-benefit ratio. In a recently published large phase 3 multicentric trial (at 133 centres) evaluating the safety and efficacy of a new oral SGLT-2 inhibitor Sotagliflozin in combination with insulin in T1DM subjects, it was found that patients who received insulin along with Sotagliflozin had better reduction of HbA1c (below 7% recommended baseline value) as compared to the group taking insulin with a placebo. But the rate of ketoacidosis and hypoglycaemia was much higher in the treatment group than the placebo group. Thus, the concomitant use of SGLT-2 inhibitors with insulin should be prescribed with caution and proper monitoring [38].
Clinical pharmacology of SGLT-2 inhibitors in heart failure
Published in Expert Review of Clinical Pharmacology, 2023
Maria Velliou, Effie Polyzogopoulou, Ioannis Ventoulis, John Parissis
The SOLOIST-WHF trial (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening HF) demonstrated that, in diabetics with a recent admission due to acute decompensated HF, treatment with sotagliflogzin 200 mg or 400 mg (dose depending on the occurrence of side effects) was associated with a lower rate of deaths from cardiovascular causes and hospitalizations for HF compared to placebo. The first dose of sotagliflozin or placebo was administered before discharge or within the first two days2 days after discharge [16]. Moreover, the SCORED study (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) also showed that sotagliflozin had a positive effect on patients with DM and chronic kidney disease and the benefit was primarily attributed to theattributed primarily to reduction in HF events. However, no decrease in cardiovascular mortality, strokesstrokes, and myocardial infarctions (MI) was observed [17].
Pharmacological treatment options for heart failure with reduced ejection fraction: A 2022 update
Published in Expert Opinion on Pharmacotherapy, 2022
Kristian Hellenkamp, Kathleen Nolte, Stephan von Haehling
As pointed out above, sotagliflozin is among the SGLT2 inhibitors recommended for patients with diabetes at risk of cardiovascular events and hospitalization of worsening HF. In this regard, the SOLOIST-WHF trial needs to be mentioned as it investigated the safety and efficacy of sotagliflozin in diabetic patients after an episode of decompensated HF with either reduced or preserved ejection fraction. Sotagliflozin is different from dapagliflozin and empagliflozin in that it also blocks some gastrointestinal SGLT1 activity and as a result delays intestinal glucose absorption. The primary endpoint of the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for HF in patients with diabetes and a recent episode of worsening HF was significantly lower with sotagliflozin than with placebo. The findings were consistent in HFrEF, HFmrEF, and HFpEF[33]. The most common adverse events, which were registered under treatment with sotagliflozin were hypotension, urinary tract infection and diarrhea[33]. Unfortunately, the trial ended after only 1,222 patients underwent randomization because it lost founding from the sponsor and therefore it ended prematurely.
Sotagliflozin and decompensated heart failure: results of the SOLOIST-WHF trial
Published in Expert Review of Clinical Pharmacology, 2021
Syed Raza Shah, Arroj Ali, Sohail Ikram
Sotagliflozin is a new novel oral antidiabetic drug that belongs to a class of sodium–glucose co-transporter 2 (SGLT2) inhibitors. This antidiabetic agent has a unique dual-receptor binding affinity for both SGLT1 the primary transporter for glucose absorption in the gastrointestinal tract and SGLT2, which is expressed in the kidney where it inhibits glucose reabsorption in the proximal tubules. Consequently, this leads to insulin-independent reduction in plasma glucose concentration, and thus has become a successful treatment option for patients with Type 2 diabetes mellitus (T2DM). However, the benefits of SGLT2 inhibitors are not limited to glycemic control. Several studies, including DAPA-HF and EMPEROR-reduced trials, have proved the efficacy of SGL2 in reducing all-cause and cardiovascular deaths in patients with HF with reduced ejection fraction (HFrEF). However, the safety and efficacy of SGLT2 inhibitors when initiated shortly after a decompensated HF event were unknown until recently, as the results of the SOLOIST-WHF Trial were made available. The trial investigates the safety and efficacy of Sotagliflozin in reducing cardiovascular events in patients with type 2 diabetes (T2DM) with recent admissions for HF.