Canalia (teneligliptin/canagliflozin) / Mitsubishi Tanabe, Daiichi Sankyo - LARVOL DELTA

Photo-Induced Sarcoidosis in a Diabetic Patient Receiving Metformin Hydrochloride. (PubMed, Case Rep Dermatol) - "A 65-year-old woman presented with numerous erythematous lesions on her eyelids, persisting for 5 months despite treatments with fexofenadine hydrochloride and topical steroids. Her medical history included diabetes mellitus and dyslipidemia, managed with rosuvastatin, metformin, and a combination of teneligliptin and canagliflozin...The patient's lesions improved 1 week after stopping metformin, enabling prednisone tapering without recurrence...In cases of refractory cutaneous sarcoidosis despite systemic steroid treatment, it is crucial to consider the coexistence of photosensitivity, particularly drug-induced photosensitivity. Therefore, carefully reviewing the patient's medication history is essential for accurate diagnosis and management."

Journal • Dermatitis • Dermatology • Diabetes • Dyslipidemia • Immunology • Inflammation • Metabolic Disorders • Sarcoidosis • IL2

Recurrent refractory candidal balanoposthitis on treatment with the antidiabetic agent: sodium-glucose cotransporter 2 inhibitor (SGLT2 inhibitor) (EADV 2024) - "He was treated with oral Itraconazole 200 mg once daily and topical 1% Clotrimazole cream...Teneligliptin/canagliflozin combination tablets were discontinued because the penile symptoms did not improve in spite of long-term antifungal therapies... SGLT2 inhibitors are prescribed more frequently in DM because of their effect on weight loss, a reduction in blood pressure, and favorable cardiovascular outcomes. However, they have a higher risk of genital mycotic infections compared with other hypoglycemic agents. Although topical therapy is usually sufficient in most cases of candidal balanoposthitis, it sometimes becomes incurable without the withdrawal of SGLT2 inhibitors like in our case."

Candidiasis • Cardiovascular • Dermatology • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Mycosis Fungoides

Combined treatment with teneligliptin and canagliflozin additively suppresses high-fat diet-induced body weight gain in mice with modulation of lipid metabolism-related gene expression. (PubMed, Eur J Pharmacol) - "These results suggest that combined treatment with teneligliptin and canagliflozin additively suppresses HFD-induced body weight gain with increasing oxygen consumption and modulating the expression of lipid metabolism-related genes. This combination therapy may provide effective body weight management for patients with T2DM and obesity."

Journal • Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Real-World Evidence of Treatment with Teneligliptin/Canagliflozin Combination Tablets for Type 2 Diabetes Mellitus: A Post-Marketing Surveillance in Japan. (PubMed, Adv Ther) - "Teneligliptin/canagliflozin combination tablets were effective and associated with an improvement in adherence without new safety concerns in Japanese patients with T2DM in real-world clinical practice."

HEOR • Journal • P4 data • Real-world evidence • Diabetes • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparison of Efficacy between Dipeptidyl Peptidase-4 Inhibitor and Sodium-Glucose Cotransporter 2 Inhibitor on Metabolic Risk Factors in Japanese Patients with Type 2 Diabetes Mellitus: Results from the CANTABILE Study. (PubMed, Diabetes Res Clin Pract) - "This study showed canagliflozin to be more effective at reducing metabolic risks than teneligliptin. In Japanese patients with T2DM and metabolic risk factors, SGLT2 inhibitors may be superior to DPP-4 inhibitors at controlling multiple metabolic risk."

Clinical • Journal • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

First report of Raspberry leaf mottle virus infecting raspberry in Poland. (PubMed, Plant Dis) - "MT241265...127:26. doi:10.1016/j.virusres.2007.03.010."

Journal • Infectious Disease

Beneficial effects of combination therapy of canagliflozin and teneligliptin on diabetic polyneuropathy and β-cell volume density in spontaneously type 2 diabetic Goto-Kakizaki rats. (PubMed, Metabolism) - "The combination therapy of DPP4i and SGLT2i improved V accompanied by PNs density and IENFD. IENFD was proportionally correlated with V. Therefore, the prevention of DPN development may be concurrently beneficial for the preservation of V in nonobese T2DM."

Combination therapy • Journal • Preclinical • Diabetes • Diabetic Neuropathy • Gene Therapies • Metabolic Disorders • Obesity • Pain • Type 2 Diabetes Mellitus

Long-term safety and efficacy of canagliflozin as add-on therapy to teneligliptin in Japanese patients with type 2 diabetes. (PubMed, Diabetes Obes Metab) - "No new safety risks with this combination were identified, and sustained improvements in HbA1c, FPG, and body weight were observed. The findings suggest that long-term co-administration of canagliflozin with teneligliptin is well tolerated and effective in Japanese T2DM patients with inadequate glycaemic control on teneligliptin alone."

Journal • Biosimilar • Diabetes

Combined Treatment with Sodium-Glucose Cotransporter-2 Inhibitor (Canagliflozin) and Dipeptidyl Peptidase-4 Inhibitor (Teneligliptin) Alleviates NASH Progression in A Non-Diabetic Rat Model of Steatohepatitis. (PubMed, Int J Mol Sci) - "CA+TE showed chemopreventive effects on NASH progression compared with single agent in non-diabetic rat model of NASH, concurrent with Ac-HSC and HCC cell proliferation, angiogenesis oxidative stress, and inflammation. Both agents are widely, safely used in clinical practice; combined treatment may represent a potential strategy against NASH."

Journal • Preclinical • CDH1

Canagliflozin may reduce gout flare risk in people with type 2 diabetes (Medicine Matters Rheumatology) - "Together, these findings 'suggest a possible protective effect for gout from an agent used for the management of diabetes and, if confirmed in dedicated prospective studies, would provide a rationale for the selective use of canagliflozin among people with type 2 diabetes who have gout or are at high risk for gout,' write Neal and coinvestigators."

Media quote

Rationale, Design, and Methods of the Study of Comparison of Canagliflozin vs. Teneligliptin Against Basic Metabolic Risks in Patients with Type 2 Diabetes Mellitus (CANTABILE study): Protocol for a Randomized, Parallel-Group Comparison Trial. (PubMed, Diabetes Ther) - "A total of 200 patients with T2DM treated with metformin alone or without glucose-lowering agents will be enrolled if they have one or more of the metabolic risk factors, such as obesity, borderline high blood pressure, and dyslipidemia...University Hospital Medical Information Network Clinical Trial Registry number: UMIN000030343. Mitsubishi Tanabe Pharma Corporation."

Clinical • Journal

The Unique Pharmacological and Pharmacokinetic Profile of Teneligliptin: Implications for Clinical Practice. (PubMed, Drugs) - "The fixed-dose combination (FDC) tablet of teneligliptin and canagliflozin has been approved in Japan; this is the first FDC tablet of a DPP-4 inhibitor and sodium glucose co-transporter 2 inhibitor in Japan, and the third globally. The FDC tablet may also provide additional prescribing and adherence benefits."

Clinical • Journal • PK/PD data • Review

COMBINED TREATMENT WITH ANTI-DIABETIC AGENTS; DIPEPTIDYL PEPTIDASE-4 INHIBITOR (DPP4-I) AND SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITOR (SGLT2-I) SUPPRESSES PROGRESSION IN NASH RAT MODEL (AASLD 2019) - "We previously demonstrated that the DPP4 inhibitor (DPP4-I) sitagliptin at a clinically comparable dose successfully ameliorated liver fibrosis through the inhibition of ERK1/2, p38, and Smad2/3 phosphorylation in activated hepatic stellate cells (Ac-HSCs). Recently, we have reported that the antidiabetic SGLT2 inhibitor (SGLT2-I) ipragliflozin significantly ameliorates liver fibrosis in diabetic rats by improving insulin sensitivity. We aimed to elucidate the effects and possible mechanisms of a DPP4-I (teneligliptin; TE) and SGLT2-I (canagliflozin; CA) combination on the progression of NASH in a rat model. In the choline deficient L-amino acid defined (CDAA) diet-induced rat model, the chemopreventive effects of TE (10mg/kg/day) and CA (10mg/kg/day) on the progression of NASH were elucidated, especially in conjunction with activated hepatic stellate cells (Ac-HSCs), oxidative stress, inflammation and angiogenesis, all known to play important roles in the progression of..."

Preclinical

Mechanistic Insights From Sequential Combination Therapy With An SGLT2 Inhibitor and DPP-IV Inhibitor: Results From the CANARIS Trial using Canagliflozin and Teneligliptin. (PubMed, Diabetes Obes Metab) - "Pharmacological anti-diabetic therapies, improving insulin resistance or secretion or its supplementation have presented some evidences to manage diabetes and to prevent its complication, however, their disadvantages such as weight gain and hypoglycemia has been reported and left as issues to be solved (1,2). Recent development of DPP-4i and GLP1RA spared of those disadvantages, probably due to inhibition of inappropriately enhanced glucagon secretion and improvement in sensitivity of insulin secretion to glucose (3,4,5)."

Combination therapy • Journal

Favorable effect of the SGLT2 inhibitor canagliflozin plus the DPP-4 inhibitor teneligliptin in combination on glycemic fluctuation: An open-label, prospective, randomized, parallel-group comparison trial (the CALMER study). (PubMed, Diabetes Obes Metab) - "Mean blood glucose decreased significantly during MTT in both groups, although the extent of the reduction was significantly greater in the COMB group (COMB, 142.3 ± 28.7 to 119.5 ± 25.1 mg/dL; SWITCH, 146.4 ± 25.5 to 135.5 ± 22.4 mg/dL, p<0.01). SGLT2i combined with DPP-4i strongly reduced the glycemic fluctuation compared with SGLT2i monotherapy."

Clinical • Journal

Concurrent Use of Teneligliptin and Canagliflozin Improves Glycemic Control with Beneficial Effects on Plasma Glucagon and Glucagon-Like Peptide-1: A Single-Arm Study. (PubMed, Diabetes Ther) - "Teneligliptin increased incretin hormones and suppressed postprandial glucagon secretion as expected. Concurrent use of canagliflozin and teneligliptin improved glycemic control without increasing postprandial glucagon secretion, and increased postprandial GLP-1 secretion and decreased the required amount of postprandial insulin secretion. The underlying mechanisms may involve canagliflozin's inhibitory activity against not only SGLT2 but also SGLT1."

Journal

Reduced Islet Parasympathetic Nerve Density Correlates with Decrease in Beta-Cell Volume of Islet in Lean Type 2 Diabetic Goto-Kakizaki Rat (ADA 2019) - "...GK was divided into DPP-4 inhibitor (DPi)-treated group (GTe) (10mg/kg teneligliptine), SGLT2 inhibitor (SGi)-treated group (GCa) (10mg/kg canagliflozin) and both treated group (GTeCa)...pvn fiber density in the islets significantly correlated with Vβ (r=0.53, p<0.01). Our results shed light on the association between terminal fiber density of pvn in the islet and Vβ, and the maintenance of the fibers may be beneficial for the prevention from Vβ loss in T2D."

Preclinical

Enhancement of Flattening Glycemic Fluctuation in Patients with Type 2 Diabetes by SGLT2 Inhibitor Combined with DPP-4 Inhibitor (ADA 2019) - "...Participants were randomized to the combination of Canagliflozin 100 mg/Teneligliptin 20 mg (C, combination) or Canagliflozin 100 mg (S, SGLT2 inhibitor) groups... SGLT2 inhibitor combined with DPP-4 inhibitor strongly flattened glycemic fluctuation compared with their single use, and this contributed to suppression of the progression of diabetic complications."

Clinical