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Allopathic Medicines
Published in Varma H. Rambaran, Nalini K. Singh, Alternative Medicines for Diabetes Management, 2023
Varma H. Rambaran, Nalini K. Singh
Symptomatic side effects that include mostly urinary or genital irritation or infections are common but tolerated by most patients. Importantly, the new SGLTi drugs have highly desirable and somewhat unexpected cardiac and renal protective effects, at least in selected cohorts. Large trials of empagliflozin (Figure 2.18a) and canagliflozin (Invokana) (Figure 2.18b), aiming to demonstrate safety in patients with T2DM and high cardiovascular risk, have shown favourable effects on heart failure, cardiovascular death, and the progression of albuminuria. Unwanted side effects, such as dehydration, lower extremity amputations, and diabetic ketoacidosis (DKA), have also been reported, but have been noted as very rare (Riddle and Cefalu 2018).Structural formulae of SGLTi drugs: (a) empagliflozin, (b) canagliflozin, (c) dapagliflozin, and (d) ertugliflozin.
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].
Efficacy and safety of ertugliflozin across racial groups in patients with type 2 diabetes mellitus
Published in Current Medical Research and Opinion, 2020
Jie Liu, Lisa Tarasenko, Annpey Pong, Susan Huyck, Larry Wu, Shrita Patel, Anne Hickman, James P. Mancuso, Ira Gantz, Steven G. Terra
The pharmacokinetic profile of ertugliflozin is similar in healthy subjects and in patients with T2DM20. Ertugliflozin exhibits a linear pharmacokinetics and dose proportionality7, with an absolute oral bioavailability of approximately 100%8, a low susceptibility to dietary effects on absorption21 and a low propensity for drug–drug interactions22. Glucuronidation by UGT1A9 and UGT2B7 is the dominant pathway of the metabolic disposition of ertugliflozin with a minor contribution from oxidative phosphorylation7,23. Genetic polymorphisms in the enzymes that metabolize ertugliflozin do not have a clinically meaningful impact on the pharmacokinetics of ertugliflozin24. No clinically meaningful racial differences were observed in the pharmacokinetics and pharmacodynamics of ertugliflozin in clinical pharmacology studies carried out in healthy subjects25,26. On the basis of these studies, no racial differences in the clinical efficacy and safety of ertugliflozin were expected in the phase III studies of patients with T2DM. The results of this current analysis are consistent with these clinical pharmacology studies.
An update of SGLT1 and SGLT2 inhibitors in early phase diabetes-type 2 clinical trials
Published in Expert Opinion on Investigational Drugs, 2019
Ernest Adeghate, Sahar Mohsin, Faisal Adi, Fares Ahmed, Ali Yahya, Huba Kalász, Kornelia Tekes, Ernest A. Adeghate
In a clinical trial involving more than 400 patients, ertugliflozin was reported to significantly reduce fasting plasma glucose, blood pressure and total body weight, 26 weeks after the administration of ertugliflozin when compared to placebo. It was particularly interesting to note that ertugliflozin was safe in patients with chronic renal disease. Moreover, hypoglycemia and infections of the urinary and genital tracts were not markedly different between treated and placebo groups [44]. However, the volume deficit that was observed in ertugliflozin-treated group [44] was higher relative to placebo. The recommended daily dose of ertugliflozin is 5–15 mg. VERTIS MONO Trial, however, showed that the rate of fungal infection of the genitalia was significantly higher in patients taking ertugliflozin when compared to placebo [45]. A randomized, double-blind, placebo-controlled interventional clinical trial (VERTIS-CV) conducted to examine the effectiveness and safety of ertugliflozin on cardiovascular outcomes in a pool of 8,000 T2DM patients are currently ongoing and will be completed in December 2019, after 6 years of intensive study [46,47]. Ertugliflozin, approved by the FDA on 22 December 2017, can be taken orally at a daily dosage of 5–15 mg. Figure 1, Table 1.
Ertugliflozin as a monotherapy for the treatment of type 2 diabetes
Published in Expert Opinion on Pharmacotherapy, 2018
Jingbo Hu, Aiping Deng, Yufen Zhao
Ertugliflozin, a novel SGLT2 inhibitor, is recommended in the USA as an adjunct to diet and exercise to improve the glycemic control in adults with T2DM, 5 ~ 15 mg once daily [9]. Given its anti-hyperglycemic mechanism, ertugliflozin can be used as an add-on therapy to other anti-diabetic agents to further improve their therapeutic outcomes. Based on the collected clinical data, ertugliflozin is effective in lowering blood glucose, moderately reducing body weight and blood pressure, are well tolerated, and do not cause weight gain and increased risk of hypoglycemia. Recently, its fixed-dose combinations, SeglurometTM (ertugliflozin + metformin) and SteglujanTM (ertugliflozin and sitagliptin), have also been approved by FDA for the treatment of T2DM [28,29]. Compared with other SGLT2 inhibitors, the selectivity of ertugliflozin for SGLT2 is higher, and it has longer half-life. However, there is no comparison of efficacy and safety for SGLT2 inhibitors, so attention to this aspect research.