Food-effect Bioavailability of Gemigliptin and Dapagliflozin 50/10 mg Fixed Dose Combination Film-coated Tablet Under Fed and Fasting Conditions in Healthy Volunteers

A Randomized, Open-label, Single-dose, Two-way Crossover Study to Investigate Food-effect Bioavailability of Gemigliptin and Dapagliflozin 50/10 mg Fixed Dose Combination Film-coated Tablet under Fed and Fasting Conditions in Healthy Volunteers

Start Date01 Jan 2022

Sponsor / Collaborator

LG Chem Ltd.

NCT04317703

/ CompletedPhase 1

A Randomized, Open-label, Single-dose, Two-way Crossover Bioequivalence Study of Fixed Dose Combination Zemimet® SR Tab. 50/1000 mg (Gemigliptin/Metformin Hydrochloride Sustained Release 50/1000 mg) and Coadministration of Zemiglo Tablet 50 mg (Gemigliptin 50 mg) and Glucophage® XR 1000 mg (Metformin Hydrochloride Prolonged Release 1000 mg) Under Fasting Conditions in Healthy Volunteers

To determine and compare the rate and extent of absorption of gemigliptin/metformin hydrochloride sustained release 50/1000 mg FDC tablet (Zemimet® SR Tab. 50/1000 mg) and coadministration of corresponding dose of gemigliptin 50 mg (Zemiglo Tablet 50 mg) and metformin hydrochloride 1000 mg prolonged release (Glucophage XR 1000 mg) as individual tablet in healthy subjects under fasting conditions

Start Date19 Aug 2020

Sponsor / Collaborator

LG Chem Ltd.

NCT04255238

/ Unknown statusPhase 3

A Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled, Parallel Group, Phase 3 Trial to Evaluate the Efficacy and Safety of Dual add-on Therapy With Gemigliptin 50 mg and Dapagliflozin 10 mg Added to Metformin Compared to add-on Therapy With Gemigliptin 50 mg in Combination With Metformin or Dapagliflozin 10 mg in Combination With Metformin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Alone

The objective of this study is to evaluate the efficacy and safety of dual add-on therapy with Gemigliptin 50 mg and Dapagliflozin 10 mg added to Metformin compared to add-on therapy with Gemigliptin 50 mg in combination with Metformin or Dapagliflozin 10 mg in combination with Metformin in patients with type 2 diabetes mellitus who have inadequate glycemic control on metformin alone

Start Date30 Jun 2020

Sponsor / Collaborator

LG Chem Ltd.

100 Clinical Results associated with Gemigliptin L-tartrate Sesquihydrate

100 Translational Medicine associated with Gemigliptin L-tartrate Sesquihydrate

100 Patents (Medical) associated with Gemigliptin L-tartrate Sesquihydrate

151

Literatures (Medical) associated with Gemigliptin L-tartrate Sesquihydrate

01 Dec 2024·Sustainable Chemistry and Pharmacy

Efficient integration of analytical quality-by-design and tri-hued HPLC-DAD approach for synchronized assessment of gemigliptin and rosuvastatin in their fixed-dose pills: Application to stability study

Author: Mohyeldin, Sara M. ; Talaat, Wael ; Kamal, Miranda F. ; Daabees, Hoda G.

Life-threatening atherosclerotic cardiovascular disorder is a well-recognized risk among diabetics, which is clin. ascribed to their unbalanced plasma lipoproteins.Gemigliptin-Rosuvastatin is a recently introduced polytherapy prescribed for the management of diabetic dyslipidemia.Currently, the main focus of several analysts is to design more ecol. friendly sustainable approaches for pharmaceutical anal.In this context, an innovative tri-hued (green, blue, and white) stability-indicating HPLC-DAD approach was developed to concurrently quantify Gemigliptin and Rosuvastatin polypills.Consequently, a strategic integration between anal. quality-by-design and green/white anal. chem. principles was specifically designed to optimize efficiency and practicality while minimizing ecol. burden.Two exptl. designs, namely two-level fractional factorial and Box-Behnken designs, were employed for screening and optimization procedures, resp.Optimal separation was attained utilizing an Agilent HC-C18 column in conjunction with a mobile phase consisting of acetonitrile and 10 mM sodium dihydrogen phosphate buffer, pH 3 (60:40 volume/volume), eluted in an isocratic manner at a 1 mL/min flow rate.Both analytes exhibited good linearities within the concentration range of 0.5-100μg/mL.Furthermore, stability studies were conducted on both drugs in response to variable stress degradation scenarios.Fortunately, the adopted approach was well-suited to resolve the studied drugs from their resp. degradants, thereby verifying the method's stability-indicating power.Tri-hued evaluation for the implemented approach was performed via up-to-date metrics, specifically, the Anal. Eco-scale, AGREE, Blue Applicability Grade Index, and RGB 12.Ultimately, our adopted stability-indicating HPLC approach exhibited great sensitivity, specificity, applicability, and rapidity as well as being ecol. sound.It is worth noting that this is the first stability-indicating HPLC approach for simultaneous assessment of the studied drugs.

01 Nov 2024·BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Gemigliptin mitigates TGF-β-induced renal fibrosis through FGF21-mediated inhibition of the TGF-β/Smad3 signaling pathway

Article

Author: Byun, Jun-Kyu ; Jung, Gwon-Soo

Fibroblast growth factor 21 (FGF21), a well-known regulator of metabolic disorders, exhibits the potential to prevent renal fibrosis by negatively regulating the transforming growth factor β (TGF-β)/Smad3 signaling pathway. Gemigliptin and other dipeptidyl peptidase-4 inhibitors are frequently used for the management of patients with type 2 diabetes. However, the protective effect of gemigliptin against renal fibrosis, particularly its potential to upregulate the expression of FGF21, remains incompletely understood. This study assessed the renoprotective effects of gemigliptin against TGF-β-induced renal fibrosis by enhancing the expression of FGF21 in the cultured human proximal tubular epithelial cell line HK-2. Treatment with FGF21 effectively prevented TGF-β-induced renal fibrosis by attenuating the TGF-β/Smad3 signaling pathway. Similarly, gemigliptin exhibited protective effects against TGF-β-induced renal fibrosis by mitigating TGF-β/Smad3 signaling through the upregulation of FGF21 expression. However, the protective effects of gemigliptin were blocked when FGF21 expression was knocked down in TGF-β-treated HK-2 cells. These results indicate that gemegliptin has the potential to exhibit protective effects against TGF-β-induced renal fibrosis by elevating FGF21 expression levels in cultured human proximal tubular epithelial cells.

01 Sep 2024·DIABETES OBESITY & METABOLISM

Dual add‐on therapy of gemigliptin and dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone: The SOLUTION 2 study

Article

Author: Kim, Kyoung‐Ah ; Park, Cheol‐Young ; Hwang, You‐Cheol ; Won, Jong Chul ; Kang, Jun Goo ; Yoo, Hye Jin ; Park, Kyong Soo ; Chon, Suk ; Moon, Shin Je ; Cho, Ho Chan ; Kim, Tae Nyun ; Cho, Eunjoo ; Han, Kyung Ah ; Kim, Jeongyun ; Choi, Sung Hee

Abstract:

Aim:

To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add‐on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add‐on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin.

Materials and Methods:

In this randomized, double‐blind, double‐dummy, active‐controlled, parallel‐group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24.

Results:

Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were −1.34% with GEMI + DAPA, −0.90% with GEMI (difference between GEMI + DAPA vs. GEMI −0.44% [95% confidence interval {CI}: −0.58% to −0.31%], P < .01) and −0.78% with DAPA (difference between GEMI + DAPA vs. DAPA −0.56% [95% CI: −0.69% to −0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection.

Conclusions:

These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well‐tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone.

News (Medical) associated with Gemigliptin L-tartrate Sesquihydrate

28 Feb 2023

·www.prnewswire.com

M8 Pharmaceuticals and Daewoong Pharmaceutical strengthen their strategic partnership by signing an exclusive licensing agreement for Envlo™ (Enavoglifozin) for Brazil and Mexico

MEXICO CITY, Feb. 28, 2023 /PRNewswire/ -- M8 Pharmaceuticals and Daewoong Pharmaceuticals announced they have signed an exclusive licensing agreement whereby M8 will have the rights to register and commercialize Envlo™ (Enavoglifozin) for Brazil and Mexico. The novel drug Envlo™ (Enavoglifozin) is a SGLT2 (sodium glucose cotransporter 2) inhibitor type diabetes treatment, and last November, it has received a regulatory approval in South Korea. Phase 3 clinical trials have been performed on type 2 diabetes patients and its results demonstrated excellent effects in dropping blood sugar level drop. The safety of Envlo™ has been confirmed and proven to show equal medicinal effect with only 0.3mg, which is 1/30 of the amount of existing SGLT2 inhibitor and has been shown to be a promising new treatment option for patients and prescribers who were unsatisfied with the blood sugar controls. It has been proven to be efficacious as a monotherapy, metformin combined modality therapy and metformin and gemigliptin or other DDP4 (Inhibitors of dipeptidyl peptidase 4) combined modality therapy. During the development of the product, Envlo™ was designated as South Korea's first drug to received a fast-track review in 2020, and is expected to be launched in South Korea by Daewoong in the first half of 2023. The Enavogliflozin monotherapy trial was a placebo-controlled superiority study. The HbA1c decreased in the Enavogliflozin group by approximately 1% over the placebo group, which was statistically significant. In addition, significant improvements were confirmed in weight, blood pressure, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared to the placebo group. The two combination trials, Enavogliflozin-Metformin and Enavogliflozin-Metformin-Gemigliptin combination, demonstrated non-inferiority in HbAc1 change compared to dapagliflozin 10 mg and its equivalent combinations. Through this agreement, Daewoong Pharmaceuticals has the plan to accelerate further overseas expansion for Enavogliflozin including China, Saudi Arabia and Russia and expand into 15 countries by 2025 and 50 countries by 2030. M8 Pharmaceuticals continues its commitment of bringing proven and innovative products to Latin American patients, and the agreement reinforces its commitment and capabilities in the area of cardiometabolism. Diabetes affects over 30 million people in Brazil and Mexico, and many of these patients continue to need better therapeutic options to optimize symptom control and improve their quality of live. According to IQVIA, the SGLT2 inhibitor market in Brazil and Mexico exceeds the 470 million USD in value and grows at a rate of more than 20% annually. "We are delighted to continue to strengthen our strategic partnership with Daewoong and see a large opportunity to address the unmet needs of millions of Latin Americans suffering from diabetes, by bringing a product like Envlo™ to the SGLT2 market with the potential to be best-in-class" stated Joel Barlan, M8's CEO. CEO Seng-ho Jeon from Daewoong Pharmaceutical stated "This contract with M8 is an example proving that Daewoong Pharmaceutical's synthetic new drugs such as Fexuclue and Envlo, are recognized as global blockbusters" and "With this contract in Central and South America as the starting point, we expect that the 36th domestically produced new drug Envlo will expand its entry into the global market in the future." About M8 PHARMACEUTICALS M8 is a specialty biopharmaceutical company focused on licensing, marketing and distributing innovative and established therapeutics in Latin America: Brazil and Mexico. We aim to become the preferred pharmaceutical partner for the licensing of high-value innovative and proven therapies across our main therapeutic areas CNS, Respiratory, Cardiometabolic, Immunology, Gastroenterology, Onco-hematology and Rare Diseases. Our mission is to provide the people of Latin America with access to the proven and innovative medicines they need to transform their lives. For further information, please visit: For more information please contact: Joel Barlan Chief Executive Officer T: +52 (55) 4431 2933 [email protected] Rafael Ferrer Vice President of Corporate Development & Strategy T: +1 (305) 299 6998 [email protected] SOURCE M8 Pharmaceuticals

Phase 3License out/inClinical ResultFast Track

15 Dec 2022

·www.fiercebiotech.com

Innovent plucks Chinese rights to LG Chem's gout disease treatment in nearly $100M deal

LG Chem's deal with Innovent comes months after the Korea-based company bought Aveo Oncology. Innovent is adding a new late-stage med to its pipeline, buying the Chinese rights to LG Chem’s phase 3 gout disease treatment for nearly $100 million. The agreement, announced Thursday, gives Innovent exclusive Chinese rights to tigulixostat, a non-purine xanthine oxidase inhibitor that manages the buildup of uric acid in patients with gout. In return, the company is paying LG Chem $10 million upfront with $85.5 million in biobucks waiting in the wings. Tigulixostat lands in Innovent’s lap with the wind in its sails after beating out both placebo and Takeda’s Uloric in uric acid reductions during a phase 2 study. LG Chem launched a phase 3 trial this quarter with the expectation of recruiting 3,000 patients across the U.S., Europe and other countries. The approval potential of the med is particularly tantalizing to Innovent given that the prevalence of hyperuricemia in China could be as high as 13.3% of the population. Another study conducted by China’s CDC found that the prevalence among adults is 11.1%. The med slides into a portfolio that includes eight approved meds in China, primarily in oncology, but a relatively thin slate of metabolic treatments. As for LG Chem, the rights handoff continues a string of deals after agreeing to buy Aveo Oncology and its approved kidney cancer drug in October for $566 million. The company noted that one of the benefits to partnering with Innovent was getting a foot in the door to the Chinese market. LG Chem’s only approved med is Zemiglo, a Type 2 diabetes treatment greenlighted for use in Korea and Thailand. Beyond tigulixostat, the company is working on treatments for nonalcoholic steatohepatitis, obesity and Type 1 diabetes.

Phase 3License out/inDrug ApprovalPhase 2Acquisition

06 Dec 2022

·www.biospace.com

Daewoong Pharmaceutical announces success in developing a new antidiabetic medication and its aims to enter the market in over 50 countries by 2030

Delivers new drug for two consecutive years by obtaining product license on "Envlo", Korea's 36th new drug from the Ministry of Food and Drug Safety Plans to enter the type 2 diabetes global market worth $71.4 billion Provides new and broad treatment options for patients with insufficient blood glucose control with three indications SEOUL, South Korea, Dec. 6, 2022 /PRNewswire/ -- Daewoong Pharmaceutical Co., Ltd. (CEO Jeon Sengho, Lee Changjae), a global healthcare company, announced on 5th that its "Envlo 0.3mg", a new sodium-glucose cotransporters 2 inhibitor (SGLT2) developed to treat type 2 diabetes mellitus obtained a product license from the Ministry of Food and Drug Safety on November 30. Envlo is indicated for monotherapy, combination therapy with Metformin and combination therapy with Metformin and Gemigliptin. SGLT2 inhibitors, which are rapidly replacing the global type 2 diabetes market worth $71.4 billion, are known to account for about $20.7 billion globally and $100 million in Korea as of 2021. Until now, the development and approval of SGLT2 inhibitors have been carried out mainly by multinational pharmaceutical companies. Daewoong Pharmaceutical, South Korea's leading healthcare company, became the first domestically to succeed in developing a new antidiabetic drug in this class by obtaining a product license. Daewoong Pharmaceutical plans to actively pursue the global market through this product. Daewoong Pharmaceutical plans to move quickly with the procedures concerning Envlo's insurance coverage and price in order to register the drug in National Health Insurance System with an indication of monotherapy, combination therapy with Metformin or Metformin & Gemigliptin in the first half of 2023. At the same time, the company has developed a roadmap to enter the global market over 10 countries including China, Brazil and Saudi Arabia by 2025 and 50 countries by 2030. The company is also running clinical trials for indication expansion while developing combination drugs. Daewoong Pharmaceutical aims to deliver the metformin combination drug in the second half of 2023, by accelerating the trial. The company estimates to achieve a cumulative three-year sale of 100 billion Korean Won. Earlier in October, Daewoong Pharmaceutical announced the Phase 3 study results of Envlo in patients with type 2 diabetes which have shown excellent hypoglycemic effect and the safety. In particular, Envlo has demonstrated its equivalent efficacy with 0.3 mg, which is less than one-thirtieth dosage of existing SGLT2 inhibitors. Its indication is also expected to provide a new treatment option for patients with insufficient blood sugar control. An official from Daewoong Pharmaceutical said, "While SGLT2 inhibitors are drawing the most attention in the global market, it is meaningful that we are the first company in Korea to develop the new diabetes medication in this class." The company official also added, "We will make our best effort to improve the quality of life of patients by providing the best-in-class antidiabetic drug. We will also contribute to the development of global pharmaceutical industry by continuously strengthening new drug development and global business through open collaboration with various partners." Meanwhile, Envlo, approved as the 36th new drug in Korea following the 34th new drug "Fexuclue" last year, listed its name as a first domestic drug to be designated for an accelerated approval by the Ministry of Food and Drug Safety in 2020. Company Codes: Korea:069620

Phase 3Drug ApprovalClinical Result

100 Deals associated with Gemigliptin L-tartrate Sesquihydrate

External Link

KEGG	Wiki	ATC	Drug Bank
-	Gemigliptin L-tartrate Sesquihydrate	A10BH06	DB12412

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	KR	LG Chem Ltd.	27 Jun 2012
Diabetes Mellitus, Type 2	KR	LG Life Sciences Ltd.	27 Jun 2012

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Noninsulin-Dependent, 2	Phase 3	-	LG Life Sciences Ltd.	17 Oct 2016
Diabetes Mellitus	Phase 1	-	LG Chem Ltd.	01 Nov 2019
Liver Diseases	Phase 1	DE	LG Life Sciences Ltd.	01 Sep 2013

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SOLUTION 2 Study (ADA2023)	Not Applicable	Add-on	469	Gemigliptin and Dapagliflozin	tpfxonslpe(ilspyyqlpg) = szuoslnpwr vqvgowgwsj (duzrqtsayp )	Positive	20 Jun 2023
				Gemigliptin	tpfxonslpe(ilspyyqlpg) = etajnpjqma vqvgowgwsj (duzrqtsayp )
NCT05663736 (Pubmed)	Phase 4	Diabetes Mellitus, Type 2	-	Gemigliptin	kudjzwlpdj(grkgppmhsz) = Gemigliptin induced favorable changes in body composition vvvkrfdnec (giepxvbgvu )	-	12 Apr 2023
				Glimepiride
FC 092 (ERA2021)	Not Applicable	Diabetic Nephropathies hemoglobinA1C \| serum bone alkaline phosphatase \| urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr ... View more	201	Gemigliptin 50 mg	wuwtygeygb(ipqkgculpd) = qdpfkctuur dgbaordcrp (ahzdarfbjo )	Positive	29 May 2021
				Placebo	wuwtygeygb(ipqkgculpd) = mqduvrfadb dgbaordcrp (ahzdarfbjo )
NCT02290301 (OPTIMUS, Pubmed \| Sci Rep)	Not Applicable	Diabetes Mellitus, Type 2	5,179	Gemigliptin	exypyqiryw(fpggzcvisl) = fwsxyqesgx cqcnkdykcm (vaarxnltna ) View more	-	04 Nov 2020
NCT02831361 (ZEUS II, Pubmed) Manual	Phase 3	Diabetes Mellitus, Type 2	283	gemigliptin	xauaxqrtnq(fpmiokqdsn): difference = -0.7 (95% CI, -0.9 to -0.4), P-Value = <0.0001 View more	Positive	01 Jan 2020
				Placebo
NCT01990469 (TROICA, Pubmed \| Diabetes Obes Metab) Manual	Phase 3	Diabetes Mellitus, Type 2	219	gemigliptin	lznlaiodom(rzsqgkwokh) = bbqiawvpmk vccldbbbnn (nczenfpeen ) View more	Positive	01 May 2017
				Placebo	lznlaiodom(rzsqgkwokh) = tybciyehwj vccldbbbnn (nczenfpeen ) View more
ASN2016	Not Applicable	toxicity from adriamycin DPP-IV \| GLP-1 \| Bax/Bcl-2 ratio ... View more	-	Adriamycin	lijxtchxbq(lvcgxnmtkd) = ebuqqyfmze kvtsbxvpnn (rdphacdcug ) View more	Positive	15 Nov 2016
				Adriamycin+Gemigliptin	lijxtchxbq(lvcgxnmtkd) = bepebtlyka kvtsbxvpnn (rdphacdcug ) View more
NCT01968044 (GUARD study, EASD2016)	Phase 3	Diabetes Mellitus, Type 2 eGFR	-	Gemigliptin	rzczemvodi(mxcddbpydc) = dbpqimrhwi tilfhqggqe (nbeqbcpgcy, 0.14) View more	Positive	13 Sep 2016
				Placebo	rzczemvodi(mxcddbpydc) = bbgweqlxta tilfhqggqe (nbeqbcpgcy, 0.14)
NCT01990469 (EASD2016)	Phase 3	Diabetes Mellitus, Type 2 Add-on	-	Gemigliptin 50 mg q.d	bdnqdrtzbx(sihmozjial) = xiwlryjbqq umltvqqvlk (boavwvgnhx, 0.17)	Positive	13 Sep 2016
				Placebo	bdnqdrtzbx(sihmozjial) = ynynqzfnci umltvqqvlk (boavwvgnhx, 0.18)
NCT01787396 (EASD2015)	Phase 3	Diabetes Mellitus, Type 2	69	Gemigliptin 50 mg	teaiotjwvx(abvbssmzfn) = reported more frequently in glimepiride group than in other groups fyofyinrtr (ryppzjfonj )	Positive	17 Sep 2015
				Sitagliptin 100 mg

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