Delving into the Latest Updates on Anagliptin with Synapse

Background:No comprehensive meta-analysis has examined and consolidated the effectiveness and safety of anagliptin in treating type 2 diabetes mellitus (T2D). To bridge this knowledge gap, we undertook this meta-analysis.Methods:Randomized controlled trials involving patients with T2D receiving anagliptin were sought after through electronic databases. The control arm consisted of either an active comparator (active control group [ACG]) or a placebo (passive control group [PCG]). The primary outcome was glycated hemoglobin (HbA1c), with secondary outcomes including fasting plasma glucose (FPG) and lipid profiles and adverse events.Results:From the 226 articles first examined, 10 randomized controlled trials with 970 participants were analyzed. Reductions in HbA1c (mean difference [MD]: −0.03%, 95% confidence interval [CI]: −0.14 to 0.14, P = .51, I2 = 9%) and FPG (MD: 0.03 mmol/L, 95% CI: −0.30 to 0.35, P = .87, I2 = 42%) were similar in the anagliptin group and ACG. Anagliptin reduced FPG better than placebo (MD: −1.25 mmol/L, 95% CI: −1.87 to −0.64, P < .0001, I2 = 0%). Sufficient data were unavailable to analyze the HbA1c lowering with anagliptin versus placebo. Among the lipid parameters, changes in total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B48, and apolipoprotein B100 were identical between the anagliptin and control groups (PCG and ACG). Anagliptin was better than ACG at lowering low-density lipoprotein cholesterol but not as good at lowering triglyceride. Adverse events were infrequent and similar in the anagliptin and control groups (PCG and ACG).Conclusion:Anagliptin positively affects glucose control and is safe for managing T2D. Its low-density lipoprotein cholesterol-lowering effect warrants further investigation.

01 Jun 2024·Diabetes, Obesity and Metabolism

Dipeptidyl peptidase‐4 inhibitor and sodium‐glucose cotransporter 2 inhibitor additively ameliorate hepatic steatosis through different mechanisms of action in high‐fat diet‐fed mice

Article

Author: Shimoda, Masashi ; Nogami, Yuka ; Kaku, Kohei ; Dan, Kazunori ; Mune, Tomoatsu ; Nakanishi, Shuhei ; Fushimi, Yoshiro ; Kimura, Tomohiko ; Kaneto, Hideaki ; Shirakiya, Yoshiko ; Sanada, Junpei ; Katakura, Yukino ; Iwamoto, Yuichiro ; Iwamoto, Hideyuki

AbstractAimDipeptidyl peptidase‐4 (DPP‐4) inhibitors suppress the inactivation of incretin hormones and lower blood glucose levels by inhibiting DPP‐4 function. Sodium‐glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels in an insulin‐independent manner by inhibiting renal reabsorption of glucose. DPP‐4 and SGLT2 inhibitors each have the potential to improve hepatic steatosis; however, their combined effects remain unclear. In this study, we examined the effects of the combination of these drugs on hepatic steatosis using high‐fat diet‐fed mice.MethodC57BL/6J male mice were fed a 60% high‐fat diet for 2 months to induce hepatic steatosis. Mice were divided into four groups (control; DPP‐4 inhibitor anagliptin; SGLT2 inhibitor luseogliflozin; anagliptin and luseogliflozin combination), and the effects of each drug and their combination on hepatic steatosis after a 4‐week intervention were evaluated.ResultsThere were no differences in blood glucose levels among the four groups. Anagliptin suppresses inflammation‐ and chemokine‐related gene expression. It also improved macrophage fractionation in the liver. Luseogliflozin reduced body weight, hepatic gluconeogenesis and blood glucose levels in the oral glucose tolerance test. The combination treatment improved hepatic steatosis without interfering with the effects of anagliptin and luseogliflozin, respectively, and fat content and inflammatory gene expression in the liver were significantly improved in the combination group compared with the other groups.ConclusionThe combination therapy with the DPP‐4 inhibitor anagliptin and the SGLT2 inhibitor luseogliflozin inhibits fat deposition in the liver via anti‐inflammatory effects during the early phase of diet‐induced liver steatosis.

19 Jan 2024·Biological and Pharmaceutical Bulletin

Effect of Anagliptin on Vascular Injury in the Femoral Artery of Type 2 Diabetic Rats

Article

Author: Matsunaga, Tamihide ; Takeuchi, Masayoshi ; Hori, Eisei ; Nagami, Chie ; Kikuchi, Chigusa ; Iwao, Takahiro ; Noda, Masato

Patients with diabetes mellitus (DM) often experience complications such as peripheral arterial disease (PAD), which is thought to be caused by vascular damage resulting from increased oxidative stress. Dipeptidyl peptidase-4 inhibitors have been reported to reduce oxidative stress, although the exact mechanism remains unclear. This study aimed to investigate the impact of long-term (6 weeks) anagliptin treatment at a dose of 200 mg/kg/d against oxidative stress in the femoral artery of Otsuka Long-Evans Tokushima Fatty (OLETF) rats using a well-established animal model for type 2 DM. Serum toxic advanced glycation end-products concentrations and blood glucose levels after glucose loading were significantly elevated in OLETF rats compared to Long-Evans Tokushima Otsuka (LETO) rats but were significantly suppressed by anagliptin administration. Plasma glucagon-like peptide-1 concentrations after glucose loading were significantly increased in anagliptin-treated rats. Superoxide production and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in femoral arteries were significantly increased in OLETF rats compared to LETO rats but were significantly decreased by anagliptin administration. The expressions of NADPH oxidase components (p22^phox in the intima region and p22^phox and gp91^phox in the media region) in the femoral artery were significantly increased in OLETF rats compared to LETO rats but were significantly suppressed by anagliptin administration. Furthermore, the femoral artery showed increased wall thickness in OLETF rats compared to LETO rats, but anagliptin administration reduced the thickening. This study suggests that long-term anagliptin administration can reduce oxidative stress in femoral arteries and improve vascular injury.

100 Deals associated with Anagliptin

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External Link

KEGG	Wiki	ATC	Drug Bank
D09780	Anagliptin	A10BH	DB12417

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	JP	Sanwa Kagaku Kenkyusho Co., Ltd.	28 Sep 2012

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Noninsulin-Dependent, 2	Preclinical	KR	JW PHARMACEUTICAL Corp.	01 May 2011
Diabetes Mellitus, Type 2	Preclinical	US	Kowa Research Institute, Inc.	01 Jul 2010

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Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02330406 (REASON, Pubmed \| Cardiovasc Diabetol)	Phase 4	Diabetes Mellitus, Type 2	353	Anagliptin	crwjyuguis(dpvosibtcs) = tlyvhbzsgt eavahqtszf (ufvzckaedq )	-	16 Nov 2019
				Sitagliptin	crwjyuguis(dpvosibtcs) = mkwmlgcvzs eavahqtszf (ufvzckaedq )
NCT02330406 (REASON, Pubmed)	Phase 4	Diabetes Mellitus	380	Anagliptin	(fenlmhadrc) = qlbdkbgwjq cudjlquuad (nasjivzugf ) View more	Positive	12 Jun 2019
				Sitagliptin	(fenlmhadrc) = nwufyhjnnx cudjlquuad (nasjivzugf ) View more
NCT01529541 (Pubmed \| Diabetes Obes Metab) Manual	Phase 3	Diabetes Mellitus, Type 2	180	Anagliptin	(bhmoobuccc) = rdjkgkmmnc scqftznxsq (nthwxoxloy, 0.70)	Non-inferior	01 May 2015
				sitagliptin	(bhmoobuccc) = zxkemvykut scqftznxsq (nthwxoxloy, 0.61)