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.

NCT04544319 / Unknown statusPhase 1

Clinical Trial to Compare the Pharmacokinetics, Safety and Tolerability of the FDC of Gemigliptin/Dapagliflozin 50/10 mg to Each Component of Gemigliptin 50 mg and Dapagliflozin 10 mg

To identify bioequivalence between Fixed-dose Combinations of Gemigliptin/Dapagliflozin 50/10 mg to Each Component of Gemigliptin 50 mg and Dapagliflozin 10 mg

Start Date01 Oct 2020

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.

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

Literatures (Medical) associated with Gemigliptin L-tartrate Sesquihydrate

05 Jan 2024·Journal of diabetes research

A Multicenter, Randomized, Open-Label Study to Compare the Effects of Gemigliptin Add-on or Escalation of Metformin Dose on Glycemic Control and Safety in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Treated with Metformin and SGLT-2 Inhibitors (SO GOOD Study)

Article

Author: Choi, Sung Hee ; Kim, Hae Jin ; Hur, Kyu Yeon ; Rhee, Eun-Jung ; Noh, Jung Hyun ; Ko, Seung-Hyun ; Jeong, In-Kyung ; Moon, Min Kyong

Background. We aimed to compare efficacy and safety between gemigliptin add-on and escalation of the metformin dose in patients with inadequately controlled type 2 diabetes mellitus (T2DM) despite treatment with metformin and SGLT2 inhibitors. Methods. This study was a multicenter, randomized, open-label, active-controlled, parallel-group comparative study. Patients with T2DM uncontrolled on metformin and SGLT2 inhibitors were randomized to receive gemigliptin 50 mg as an add-on (GEM group,

n = 37

) or escalation of the metformin dose (500 mg, MET group,

n = 38

) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to week 24. Results. At weeks 12 and 24, the reduction in HbA1c levels was significantly greater in the GEM group than in the MET group (GEM vs.

MET = - 0.64 % \pm 0.34 %

vs.

- 0.36 % \pm 0.50 %

p = 0.009

at week 12;

- 0.61 % \pm 0.35 %

vs.

- 0.33 % \pm 0.70 %

p = 0.045

at week 24). The proportions of patients who achieved target HbA1c levels of <7.0% at weeks 12 and 24 and <6.5% at week 12 were greater in the GEM group than in the MET group. An index of β-cell function was also significantly improved in the GEM group. The safety profiles were similar between the two groups. Conclusions. Gemigliptin add-on therapy may be more effective than metformin dose escalation in patients with T2DM insufficiently controlled using metformin and SGLT2 inhibitors, without safety concerns. This trial is registered with CRIS_number: KCT0003520.

08 Dec 2023·Medicine

The effect of gemigliptin treatment on immune parameters including regulatory T cells in patients with type 2 diabetes and moderate to very severe chronic renal impairment

Article

Author: Kim, Yanghyeon ; Rim, Hark ; Lee, Nagyeom ; Shin, Ho Sik ; Jung, Yeonsoon ; Kim, Ye Na ; Heo, Sujung

It is crucial to understand the impact of DPP-4 inhibitors on the immune system, particularly T cell differentiation, maturation, and proliferation, in patients with type 2 diabetes and CKD. This prospective observational study aimed to investigate the distribution of immune cells (particularly regulatory T cells), following the administration of gemigliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus and chronic kidney disease. We enrolled 28 patients with type 2 diabetes, aged 20 to 69, who had been taking a daily dose of 50mg gemigliptin for <3 months and had chronic kidney disease stages 3, 4, or 5, including that undergoing dialysis. T regulatory cells were defined as CD4 + CD25 high CD127 low/- FoxP3 + phenotype, and flow cytometry was used to examine the distribution of T regulatory cells. In the patient group, blood samples were collected at baseline, as well as at 3 and 6 months after initiating medication. Of the 28 patients, 17 (60.7%) were male and the mean age was 61.82 ± 8.03 years. Serum Cr ≥ 1.5 mg/dL was 16 (57%), and Cr < 1.5 mg/dL was 12 (43%). The number of CD4(+)/CD25(+) cells did not significantly increase or decrease in baseline, 3 months, and 6 months time changes, and the number of CD127(-/FoxP3(+) cells did not change significantly. Treatment with gemigliptin for 3 and 6 months did not significantly alter the number, percentage, or ratio of circulating Treg cells in patients with type 2 diabetes and CKD. Therefore, the administration of gemigliptin may help maintain regulatory T cells or have no significant impact.

01 Dec 2023·Molecular metabolism

Gemigliptin, a DPP4 inhibitor, ameliorates nonalcoholic steatohepatitis through AMP-activated protein kinase-independent and ULK1-mediated autophagy

Article

Author: Lee, Yoonjin ; Do, In-Gu ; Kim, Sung-Ho ; Song, Youngmi ; Yang, Hyekyung ; Park, Cheol-Young ; Kim, Juhee

OBJECTIVE:

Abnormal autophagic function and activated inflammasomes are typical features in the liver of patients with non-alcoholic steatohepatitis (NASH). Here, we explored whether gemigliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor for treatment of type 2 diabetes, can induce autophagy and regulate inflammasome activation as a potential NASH treatment independent of its anti-diabetic effect.

METHODS:

Expression analysis was performed using human liver samples obtained from 18 subjects who underwent hepatectomy. We explored the function and mechanism of gemigliptin using a methionine- and choline-deficient diet (MCD)-induced NASH mouse model and HepG2 cells cultured in MCD-mimicking medium.

RESULTS:

Autophagy was suppressed by marked decreases in the expression of ULK1 and LC3II/LC3I ratio in human NAFLD/NASH patients, a NASH mouse model, and HepG2 cells cultured with MCD-mimicking media. Surprisingly, we found that the expression of p-AMPK decreased in liver tissues from patients with steatosis but was restored in NASH patients. The expression of p-AMPK in the NASH mouse model was similar to that of the control group. Hence, these results indicate that autophagy was reduced in NASH via an AMPK-independent pathway. However, gemigliptin treatment attenuated lipid accumulation, inflammation, and fibrosis in the liver of MCD diet-fed mice with restoration of ULK1 expression and autophagy induction. In vitro, gemigliptin alleviated inflammasome activation through induction of ULK1-dependent autophagy. Furthermore, gemigliptin treatment upregulated ULK1 expression and activated AMPK even after siRNA-mediated knockdown of AMPKα1/2 and ULK1, respectively.

CONCLUSIONS:

Collectively, these results suggest that gemigliptin ameliorated NASH via AMPK-independent, ULK1-mediated effects on autophagy.

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 Life Sciences Ltd.	27 Jun 2012
Diabetes Mellitus, Type 2	KR	LG Chem 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

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	pcwrbytzid(cpasuuynrt) = cskccsqhky eoiparvfkb (otrcenkmuo )	Positive	20 Jun 2023
				Gemigliptin	pcwrbytzid(cpasuuynrt) = hqjgjysidm eoiparvfkb (otrcenkmuo )
NCT05663736 (Pubmed)	Phase 4	Diabetes Mellitus, Type 2	-	Gemigliptin	gwasjddtar(cgydgixzts) = Gemigliptin induced favorable changes in body composition bzgjqvmqtl (vaexiwidqu )	-	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	aipxneczmx(svkllkwhnk) = biogqjwizp epkwmyxndz (lqgkhgmist )	Positive	29 May 2021
				Placebo	aipxneczmx(svkllkwhnk) = vnjzwvidfd epkwmyxndz (lqgkhgmist )
NCT02290301 (OPTIMUS, Pubmed \| Sci Rep)	Not Applicable	Diabetes Mellitus, Type 2	5,179	Gemigliptin	mftxeeuews(uczrkcusti) = syufkylkay ogipxqpdlz (vobpjmydap ) View more	-	04 Nov 2020
NCT02831361 (ZEUS II, Pubmed) Manual	Phase 3	Diabetes Mellitus, Type 2	283	gemigliptin	okmwygvces(rzvbckflhe): 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	obfzgyatzg(ymnmxbgqgz) = nyfynnegdh elitgiyeyl (ayzpcwmhtp ) View more	Positive	01 May 2017
				Placebo	obfzgyatzg(ymnmxbgqgz) = uxncrplaqm elitgiyeyl (ayzpcwmhtp ) View more
ASN2016	Not Applicable	toxicity from adriamycin DPP-IV \| GLP-1 \| Bax/Bcl-2 ratio ... View more	-	Adriamycin	dbvrqjmlhm(ddhxpksexg) = nvyztscata vgftklwnux (hkasxxkdkq ) View more	Positive	15 Nov 2016
				Adriamycin+Gemigliptin	dbvrqjmlhm(ddhxpksexg) = jxrpndhpso vgftklwnux (hkasxxkdkq ) View more
NCT01990469 (EASD2016)	Phase 3	Add-on	-	Gemigliptin 50 mg q.d	xfesgdfbfw(vvqrqicuij) = gmomiranvx gzoturnfqm (vywtffvgtv, 0.17)	Positive	13 Sep 2016
				Placebo	xfesgdfbfw(vvqrqicuij) = cnpvncydhq gzoturnfqm (vywtffvgtv, 0.18)
NCT01968044 (GUARD study, EASD2016)	Phase 3	Diabetes Mellitus, Type 2 eGFR	-	Gemigliptin	onvhmmrcnn(rmgydtfhvk) = pgjocpkmrn hpjgdagyiq (yfznjxwrrq, 0.14) View more	Positive	13 Sep 2016
				Placebo	onvhmmrcnn(rmgydtfhvk) = syiqasznwp hpjgdagyiq (yfznjxwrrq, 0.14)
NCT01968044 (Phase 3b, EASD2015)	Phase 3	HbA1c \| eGFR \| urinary albumin creatinine ratio ... View more	132	Gemigliptin	fqbfbdgwlw(szvjkwylnt) = ddlfdyznix xefthzscbj (igmcdahqwk, 0.14)	Positive	17 Sep 2015
				Placebo	fqbfbdgwlw(szvjkwylnt) = hpvgclfkse xefthzscbj (igmcdahqwk, 0.14)

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