Delving into the Latest Updates on Linagliptin with Synapse

Elevated levels of dipeptidyl-peptidase (DPP-4) enzyme, associated with accelerated bone resorption, are linked to both post-menopausal osteoporosis (PMO) and glucocorticoid-induced osteoporosis (GIO). Consequently, DPP-4 inhibitors, a class of anti-diabetic drugs, emerge as potential candidates for repurposing as anti-osteoporotic agents. In this study, we explored the effect of 4-week treatment with linagliptin (a DPP-4 inhibitor) and its combination with metformin on PMO and GIO in mice. PMO was induced in Balb/c mice by injecting 4-vinyl cyclohexene diepoxide (VCD), 160 mg/kg, ip for 15 days while GIO was induced by administering dexamethasone (DEX) 5 mg/kg, ip for 21 days. A significant improvement in bone architectural parameters and bone mineral density (BMD) was observed following the linagliptin-metformin combination, which was consistent with the altered bone turnover markers i.e., increased ALP, osteocalcin, BMP-2, and reduced serum calcium, TRAP, sclerostin and pro-inflammatory cytokines. Results from bone immunohistochemistry (IHC) demonstrated that the combination led to an increase in immunopositive OPG cells, while RANKL expression was diminished. Linagliptin, however, demonstrated only partial improvement in the PMO model. Conversely, in the GIO model, linagliptin did not show a significant effect except for improved BMD and sclerostin levels. Treatment with metformin did not show significant changes in either model. These findings suggest that the combination of linagliptin with metformin could alleviate the PMO and GIO, possibly through targeting AMPK and Wnt signaling pathway and thereby modulating BMP-2, sclerostin and RANKL/OPG.

01 Sep 2025·BIOMATERIALS

Regulation of osteoimmune microenvironment via functional dynamic hydrogel for diabetic bone regeneration

Article

Author: Qin, Yi ; Yu, Lei ; Li, Wenming ; Geng, Dechun ; Xia, Wenyu ; Yin, Weiling ; Li, Wenhao ; Zhang, Wei ; Yang, Peng ; Ding, Fan ; Meng, Fanwen ; Ge, Gaoran ; Wu, Zebin ; Chen, Xu ; Bai, Jiaxiang

Bone regeneration and repair face formidable challenges under diabetic conditions, primarily due to the disruption of macrophage polarization induced by diabetes and the inflammatory imbalance within the bone microenvironment. We have developed a novel dynamic hydrogel system (AG-CD@LINA), constructed through the coordination crosslinking of thiolated gelatin (SH-Gelatin) and gold ions (Au³⁺), followed by grafting with cyclodextrin to load the ligand linagliptin. This hydrogel effectively inhibits the formation of M1 macrophages and the expression of pro-inflammatory cytokines by gradually releasing linagliptin. Simultaneously, it promotes the formation of M2 macrophages and the expression of anti-inflammatory cytokines, thus improving the inflammatory microenvironment of diabetic bone defects. Consequently, it facilitates the migration of mesenchymal stem cells and angiogenic cells, augments osteogenic activity, and promotes vascularization, collectively accelerating the regeneration of diabetic bone tissue. Mechanistically, polarization occurs through the TLR3-NF-κB signaling pathway. In vivo experiments demonstrate that the in-situ injection of the hydrogel enhances the regeneration of bone tissue and the restoration of bone structure in diabetic bone defects, effectively modulating local inflammation and promoting vascular formation. This study suggests that functionalized dynamic hydrogels can improve the inflammatory microenvironment by regulating in situ macrophage polarization, thereby facilitating the reconstruction of bone microstructure. This approach represents a promising novel therapeutic strategy for diabetic bone defects.

01 Sep 2025·TALANTA

Simultaneous enantiomeric separation of linagliptin and clopidogrel by capillary electrophoresis for the individual, combined, and enantiomeric ecotoxicity evaluation on Pseudokirchneriella subcapitata

Article

Author: Marina, María Luisa ; García, María Ángeles ; Boltes, Karina ; García-Cansino, Laura

An analytical methodology was developed in this work enabling the simultaneous enantioseparation of linagliptin and clopidogrel by Capillary Electrophoresis (CE). The use of 10.4 mg/mL carboxymethyl-β-CD (CM-β-CD) as chiral selector in 25 mM phosphate buffer (pH 7.0), at 25 °C and a separation voltage of 30 kV, made possible the chiral separation in 7.4 min, with resolution values of 3.9 and 2.7 for linagliptin and clopidogrel enantiomers, respectively. The analytical characteristics of the developed methodology were evaluated in terms of linearity, precision, trueness, LODs and LOQs, and found adequate for the enantiomeric determination of both drugs. The method was applied to study the stability under abiotic and biotic conditions and the ecotoxicity of both drugs on Pseudokirchneriella subcapitata at individual, combined, and enantiomeric level. Both studies were carried out for each enantiomer of linagliptin, racemic linagliptin, S-clopidogrel, racemic clopidogrel, a mixture of the active enantiomers (R-linagliptin and S-clopidogrel), and a mixture of both racemates. Results obtained showed that individual solutions of S-linagliptin, R-linagliptin, S-clopidogrel, RS-linagliptin, and a mixture of the active enantiomers of both compounds, were stable under abiotic and biotic conditions, regardless of the incubation time; however, the concentration of racemic clopidogrel after 96 h of incubation showed a decay which ranged from 18 to 24 % under abiotic and biotic conditions, respectively. Experimental determination of ecotoxicological parameters demonstrated that all compounds studied (individual enantiomers, racemates, the combination of active enantiomers, and racemic mixtures) are highly toxic to algae. In mixtures, different degrees of antagonisms and synergism were observed.

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News (Medical) associated with Linagliptin

09 May 2025

·pharma.economictimes.indiatimes.com

NPPA sets Empagliflozin combos retail prices, as domestic brands initiate generic contest

New Delhi: As domestic brands in India began introducing their generic versions of key anti-diabetic medicine empagliflozin following the expiry of its patent, the National Pharmaceutical Pricing Authority (NPPA), has fixed the retail prices of the drug combinations and different dosage strengths. Issuing a gazette notification, the Ministry of Chemicals and Fertilizers and the country’s drug price regulator announced that “based on the decision of 132nd Authority meeting dated 29.4.2025 the authority has fixed retail prices of 84 formulations under Drugs (Prices Control) Order, 2013.” The price list attached with the official notification includes around 36 variants of empagliflozin, linagliptin and metformin hydrochloride Fixed-Dose Combinations (FDC) of various brands and manufacturers. Empagliflozin, indicated for Type-2 diabetes, inhibits the release of SGLT2 protein in the kidneys which reduces glucose reabsorption in blood and helps in lowering the blood sugar level of patients. Under the notified list the combination of empagliflozin 12.5mg and metformin hydrochloride 1000mg tablet of Corona Remedies is priced at ₹19.64, while a combination including linagliptin along with these active ingredients of Lupin is priced at ₹22.32. The notified retail prices excludes the applicable Goods and Services Tax (GST) and are applicable to the respective manufacturer and marketer specified in the list. As per a market research firm Pharmarack as of April 2025 the total market of empagliflozin and its related combination is valued around ₹745 crore. Of this, plain empagliflozin and its combination with linagliptin accounts for nearly 86 per cent of the total market. In FY25 empagliflozin plain tablets reported a Moving Annual Turnover of ₹337 crore, reflecting a market share of 45 per cent while its combination version with linagliptin had a MAT value of ₹308 crore and a market share of 41 per cent. Besides this the drug's other combinations such as empagliflozin and metformin reported an annual turnover of ₹102 crore with a 14 per cent market share. The retail price fixation exercise has been undertaken in the aftermath of the expiry of empagliflozin’s patent in March this year followed by a series of generic entrants in the market. In India, the drug patent was owned by Germany-based Boehringer Ingelheim and the drug was marketed under the brand name Jardiance. After the drug went off patent, companies like Alkem and Glenmark launched their generic versions under the brand names ‘Empanorm’ and ‘Glempa’ respectively. Besides them other major generic players like Mankind and USV also joined the fray. For patients, the development gave a major price relief as the generic versions are stated to cost around 80-90 per cent less than the patented version. As per the NPPA price list the innovator's version single tablet is priced at ₹53, whereas the other brands from the license holders Torrent, Cipla and Lupin are priced between ₹46-48 per tablet. While announcing the launch, Rajeev Juneja, Vice Chairman and Managing Director, Mankind Pharma said that, “the company will market its respective brand at ₹5.49 per tablet for the 10 mg variant and ₹9.90 per tablet for the 25 mg variant. The latest monthly progress report of Indian pharma market by Pharmarack suggests that as of April close to 147 brands from 37 companies have forayed in the empagliflozin plain and combinations market, reflecting a two-fold jump from the previous month status of 86 brands and 19 Companies. Under the provisions of Drugs (Prices Control) Order, 2013, the retail price of a new drug is fixed by NPPA and the applicant manufacturer and marketer, are required to sell the new drug within the notified price. By Abhijeet Singh ,

09 May 2025

·pharma.economictimes.indiatimes.com

Generic versions of key diabetic drug in market double in a month

New Delhi: In less than two months after diabetes drug Empagliflozin went off patent, Indian branded generic players have crowded the market with their versions of the product leading to a month-on-month doubling in the number of players and brands flooding the market in April. Nearly 147 brands of the drug and 37 companies are in the market now, up from 86 brands and 19 companies in March, according to data from industry tracker and market researcher PharmaTrac. Doctors said that an increasing number of anti-diabetic drugs going off patent-with Empagliflozin being the latest-is good for patients and medical practitioners as it makes anti diabetes drugs more affordable in India where cases of diabetes are rising. Empagliflozin-which was Boehringer Ingelheim's innovator drug sold under the brand name Jardiance-went off patent mid-March. It is used to improve glucose control in people with Type 2 diabetes. "With almost 150 brands and 40 companies jumping in the Empagliflozin off patent opportunity and volume sales picking up steeply in the last two months, every player in the IPM (Indian pharmaceutical market) looks like geared up to make the most of this opportunity," said Sheetal Sapale, vice president, commercial, PharmaTrac. "Most of the innovator molecules (used to treat Type 2 diabetes) in SGLT 2 (Sodium-Glucose Co-Transporter-2) and DPP4 i (Dipeptidyl peptidase-4 inhibitors) have gone off patent... creating many affordable options available to eligible Indian masses through branded generics ," she added. Empagliflozin is an SGLT-2 inhibitor . Others in the same group include dapagliflozin-whose patent expired a couple years ago leading to nearly 200 generic brands coming into the market. Companies such as Alkem Laboratories , Glenmark Pharmaceuticals and Mankind Pharma launched their versions of Empagliflozin, and slashed prices to about ₹5 per unit, which is 80-90 per cent lower than the innovator's prices. "Ever since dapagliflozin has gone off patent, many more people have access to it has become cheaper. Empagliflozin is also similar to it...it's a good medicine for sugar, gives some protection to the heart and kidney too," said Dr David Chandy, director-endocrinology & diabetology at Sir H N Reliance Foundation Hospital and Research Centre. More such molecules going off patent increases the reach to larger populations. "Earlier when only the innovators had these molecules, maybe 2-5 per cent of India's diabetic population could afford it, now the entire diabetic population can afford it," said Chandy. Empagliflozin is a ₹745 crore market today with plains contributing to almost 45 per cent in terms of value as well as quantity. Empagliflozin plain and Empagliflozin plus Linagliptin contribute nearly 80 per cent of this. "In the long-term, more and more affordable medication options are good for patients with the cases of diabetes spiralling in the country and doctors have more ammunition or options for treatment now compared to 5-10 years back," said Chandy. "What will be interesting in the diabetes scenario is that in the next six months, once semaglutide goes off patent, there will be a paradigm shift for diabetes treatment once it is available at a low price," he said. By Rica Bhattacharyya ,

09 Apr 2025

·pharma.economictimes.indiatimes.com

As Empagliflozin goes off patent, 71 copies of the key diabetes drug roll out in a month

New Delhi: Less than a month after diabetes drug Empagliflozin (Jardiance) lost its patent, 71 new brands have flooded the market and 17 companies have launched their versions. An analysis by Pharmarack, a market research firm, showed that the pickup has been significant after the drug went off patent. "Empagliflozin off patent opportunity has been voraciously grabbed by many players in the Indian pharmaceutical market . When the molecule went off patent the pickup was significant. The market now operates with 86 brands from 19 companies. A significant 71 are new brands," said Sheetal Sapale, vice president, commercial, Pharmarack. Sales have increased to 7.8 million units per month from 5.5 million, she said, adding that many companies have followed a multi-brand and multi-division strategy to ensure rapid gains. "A sharp increase in units is a strong indicator of the price differential in the branded generics," Sapale added. The move follows the expiration of Boehringer Ingelheim 's patent on Empagliflozin on March 11. The company sold Empagliflozin under the brand name Jardiance. Companies such as Alkem Laboratories , Glenmark Pharmaceuticals and Mankind Pharma launched their versions of Empagliflozin, with 80-90 per cent lower prices than the innovator's. Prices have fallen up to ₹5 per unit from ₹60-70 earlier. Prices of Empagliflozin combinations have also gone down. For instance, Empagliflozin plus Linagliptin has seen an almost 80% drop in price while Empagliflozin plus Metformin has seen almost 73% decline. "The drop in price is something which makes this product more affordable and more reachable for the masses," Sapale said. She said the drug might be made available by more companies and brands in the coming months. "In the second month after the patent expiry, it is possible that we may capture many more brands and many more companies in this market. But typically, what we have seen is the first mover advantage that makes the brand make it bigger," Sapale said. "So, whatever companies or brands that have got launched in month one, they would be the ones which would take away the major market share or major buy in this branded, generic segment." By Teena Thacker ,

Patent Expiration

100 Deals associated with Linagliptin

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KEGG	Wiki	ATC	Drug Bank
D09566	Linagliptin	A10BH05	DB08882

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	United States	Boehringer Ingelheim Pharmaceuticals, Inc.	02 May 2011

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Stiffness	Phase 3	Netherlands	Boehringer Ingelheim GmbH	01 Mar 2014
Albuminuria	Phase 3	United States	Eli Lilly & Co.	01 Feb 2013
Albuminuria	Phase 3	United States	Boehringer Ingelheim GmbH	01 Feb 2013
Albuminuria	Phase 3	Japan	Eli Lilly & Co.	01 Feb 2013
Albuminuria	Phase 3	Japan	Boehringer Ingelheim GmbH	01 Feb 2013
Albuminuria	Phase 3	Canada	Boehringer Ingelheim GmbH	01 Feb 2013
Albuminuria	Phase 3	Canada	Eli Lilly & Co.	01 Feb 2013
Albuminuria	Phase 3	Denmark	Eli Lilly & Co.	01 Feb 2013
Albuminuria	Phase 3	Denmark	Boehringer Ingelheim GmbH	01 Feb 2013
Albuminuria	Phase 3	Finland	Boehringer Ingelheim GmbH	01 Feb 2013

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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


NCT03194945 (Literature) Manual	Phase 4	Diabetes Mellitus, Type 2	412	Linagliptin plus Metformin	ywolvrknuh(oidmsedgrg) = jersvlhvpo mnbzxfkpco (bxypynsziz ) View more	Positive	15 Oct 2024
				Linagliptin	ywolvrknuh(oidmsedgrg) = kktyhmtofw mnbzxfkpco (bxypynsziz ) View more
ATS2024	Not Applicable	-	-	Linagliptin 5 mg	lsghwaauzc(eevvekzfiz) = Severe hyponatremia (serum sodium concentration below120 mEq/L) can cause seizure, coma, and death. Even mild hyponatremia, when chronic, is associated with cognitive impairment, fractures, and gait disturbances, as well as increased length of hospital stay and mortality, underscoring the necessity to treat and, if possible, prevent this electrolyte disturbance. dxzgzthnap (znvppmspen ) View more	-	19 May 2024
				Insulin glargine 8 units nightly
NCT03470454 (Pubmed \| Ren Fail)	Not Applicable	Acute Kidney Injury	800	N-acetyl cysteine and saline	kovoypfhnx(lfyqqomhpw) = pdutpajxei lnhymgrdwb (ntboyminqr )	-	31 Dec 2023
				Allopurinol	kovoypfhnx(lfyqqomhpw) = gkcjmbrkwg lnhymgrdwb (ntboyminqr )
NCT04564872 (HSK7653, EASD2023)	Phase 3	Diabetes Mellitus, Type 2 Add-on	-	HSK7653 10mg	titlrbazzg(wuyjutyikh) = igzvkzufjr cahadmzamf (buzpvxaima, -1.08 to -0.83)	Positive	03 Oct 2023
				HSK7653 25mg	titlrbazzg(wuyjutyikh) = uijvfmdzis cahadmzamf (buzpvxaima, -1.12 to -0.87)
ADA2023	Not Applicable	Prediabetic State	658	Metformin monotherapy	mpsvxfnkay(kmexeviesd) = jobqxzvhjp weeyteizby (wmhdhunamp ) View more	-	20 Jun 2023
				Linagliptin monotherapy	xiqitcdewo(rwzpaeyizl) = xmhmkhojzm fptubivian (bozrbcvnrz )
NCT02372630 (1971, CTgov)	Phase 4	Insulin Resistance \| Inflammation \| stress oxidative ... View more	40	Placebo (Placebo)	ndixkxpedk(srnddjbgwu) = loxvetisay umihmpkohj (csexljymku, 0.148) View more	-	21 Feb 2023
				Linagliptin (Linagliptin 5mg Per Day)	ndixkxpedk(srnddjbgwu) = tmhenolvao umihmpkohj (csexljymku, 0.129) View more
NCT02467478 (CTgov)	Phase 4	Diabetes Mellitus, Type 2 \| Renal Insufficiency	31	Placebo (Placebo)	ojnzhmloeo(pvfrjrwtfn) = agoemfitks kmpvddxsbv (pedexucobg, 1.11) View more	-	19 Jan 2023
				Linagliptin (Linagliptin)	ojnzhmloeo(pvfrjrwtfn) = qnbrozbhzq kmpvddxsbv (pedexucobg, 2.80) View more
ADA2022	Not Applicable	Diabetes Mellitus, Type 2	100	Linagliptin	qpjpylfibs(qbeojtwcqn) = teugokqeff xnieyafrqy (icffvosxya )	-	01 Jun 2022
				Sitagliptin	qpjpylfibs(qbeojtwcqn) = dowjthnncw xnieyafrqy (icffvosxya )
NCT01650259 (Pubmed \| Expert Opin Drug Saf)	Not Applicable	Diabetes Mellitus, Type 2	4,876	linagliptin (BMI <25 kg/m2)	iiqmtdmeej(bcbksogzpb) = dtfwbttfzw zryodcimey (xtwzotcbza ) View more	-	14 Apr 2022
				linagliptin (BMI 25 to <30 kg/m2)	iiqmtdmeej(bcbksogzpb) = lrsqccidme zryodcimey (xtwzotcbza ) View more
NCT04542213 (Pubmed \| Sci Rep)	Phase 3	COVID-19	73	Linagliptin + insulin	ncvqykkwkv(qkmsnroplf) = No major side effects were observed roxdabwqsf (dcftqvuxzb )	Positive	11 Jan 2022
				Insulin alone