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Endocrine Disorders, Contraception, and Hormone Therapy during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
No human studies of linagliptin during pregnancy are published. The manufacturer provides the only information on linagliptin use during gestation. Placental transfer has not been analyzed for linagliptin, but the long-elimination half-life, molecular weight and charge suggest it will cross the placenta. At doses, nearly 2,000 times the usual human dose given to pregnant rabbits and rats during embryogenesis, no increased frequency of congenital anomalies was reported. The theoretical but probably real risk of hypoglycemia neonatally and during breastfeeding should be monitored. Pregnancy outcome was available for 14 of 33 exposures to linagliptin. Of the 14, two major congenital anomalies were observed (patent ductus and holoprosencephaly) were observed (Benhalima et al., 2018).
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.
Management of Obesity-Associated Type 2 Diabetes
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
Wanda C. Lakey, Lillian F. Lien, Mark N. Feinglos
DPP-IV inhibitors slow the action of endogenous DPP-IV enzymes and subsequently prolong the effects of endogenous GLP-1. Thus, DPP-IV inhibitors promote glucose-dependent increases in insulin secretion and glucose-dependent suppression of glucagon secretion. Available DPP-IV inhibitors include sitagliptin, saxagliptin, linagliptin, and alogliptin. DPP-IV inhibitors are weight-neutral. Hypoglycemia can occur with DPP-IV inhibitors when combined with agents known to cause hypoglycemia, such as sulfonylureas or insulin. An increased risk of infections, such as upper respiratory infections and nasopharyngitis, has been reported with DPP-IV inhibitor use. Post-marketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic and necrotizing pancreatitis, have also been reported [149]. Dose adjustments are required with renal impairment, with the exception of linagliptin. An increase in hospitalizations for heart failure has been observed with patients receiving saxagliptin [156] and alogliptin [157]. Caution should be utilized when prescribing these medications to individuals at risk for heart failure.
Long-term safety and effectiveness of linagliptin as add-on therapy in Japanese patients with type 2 diabetes: final results of a 3-year post-marketing surveillance
Published in Expert Opinion on Drug Safety, 2021
Tomohiro Ito, Yusuke Naito, Naoki Shimmoto, Kaori Ochiai, Naoyuki Hayashi, Tomoo Okamura
Subgroup analyses for primary endpoints, secondary endpoints, and change from baseline in HbA1c over time were conducted according to baseline concomitant antidiabetic drug and baseline age (<65 years, 65–<75 years, ≥75 years). Patients who had been prescribed linagliptin in combination with ≥2 other antidiabetic drugs at baseline were included in each concomitant antidiabetic drug subgroup. In addition, change from baseline in HbA1c over time was also analyzed in a subgroup of patients who started linagliptin in combination with another antidiabetic drug and had no change in concomitant antidiabetic drug regimen and dose during the observation period. Patients who were treated with fixed-dose combination drugs at baseline were excluded from the subgroup analyses by concomitant antidiabetic drug because it was impossible to determine which ingredients in the fixed-dose combination were responsible for the effect. Similarly, no subgroup analysis for effectiveness was conducted in patients who were treated with GLP-1 receptor agonists (GLP-1RAs) or DPP-4is at baseline because these agents had the same antidiabetic mechanisms as linagliptin.
Linagliptin in patients with type 2 diabetes and cardiovascular and/or renal disease: results from a cardiovascular and renal outcomes trial
Published in Postgraduate Medicine, 2020
During a median follow-up of 2.2 years, patients allocated to linagliptin demonstrated no increase in the risk of 3P-MACE versus placebo: hazard ratio (HR) 1.02 [95% confidence interval (CI) 0.89–1.17]; P < 0.001 for non-inferiority, with no difference between linagliptin and placebo for any of the MACE endpoints (CV death, nonfatal MI, or nonfatal stroke). Additionally, linagliptin did not increase the risk of all-cause mortality (HR 0.98 [0.84–1.13]) or the risk of non-CV death (HR 1.02 [0.78–1.33]) in this high-risk patient population [13]. There was also no increase in the risk of hospitalization for HF for linagliptin versus placebo (HR 0.90 [0.74–1.08]), regardless of history of HF or kidney disease at baseline [12]. The relatively high event rate for hospitalization for HF (209 events [6.0%] linagliptin, 226 events [6.5%] placebo) [13] is consistent with the high-risk population enrolled in the trial. The CV safety of linagliptin was demonstrated across patient subgroups.
The combination of linagliptin and metformin rescues bone loss in type 2 diabetic osteoporosis
Published in Journal of Drug Targeting, 2023
Jing Liu, Zhihong Liu, Ming Lu, Yanrong Zhang
Metformin, in addition to lowering blood sugar, has been demonstrated in many prior studies and clinical results to enhance bone mineral density (BMD), reducing osteoporosis in T2DM patients [8]. Metformin has recently been discovered to protect osteoblasts and boost bone forming [9]. The action and effect of metformin on T2DM induced osteoporosis, however, remain unknown. Metformin has been shown to inhibit the TLR4 signalling pathway in the skeletal muscle tissue thereby improving the differentiation of osteoblast in T2DM rats [10]. Linagliptin is a Dipeptidyl peptidase 4 inhibitor that has been licenced for the treatment of T2DM. Linagliptin has hypoglycaemic effects and is thought to have potential cardiovascular and renal advantages [11].