Mechanistic insights from sequential combination therapy with a sodium glucose co‐transporter‐2 inhibitor and a dipeptidyl peptidase‐4 inhibitor: Results from the CANARIS Trial using canagliflozin and teneligliptin

Okahata, Sumie; Sakamoto, Kei; Mitsumatsu, Takako; Kondô, Yûkô; Tanaka, Shoji; Shiba, Teruo

doi:10.1111/dom.13505

Cited by 4 publications

(4 citation statements)

References 22 publications

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“…The efficacy of the empagliflozin ? linagliptin FDC was also evaluated in drug-naı ¨ve patients [46][47][48][49][50] Certain anecdotal studies have been conducted in Japan on the effect of sequential therapy with a combination of canagliflozin and teneligliptin in patients with T2DM [46,47]. However, since the FDC has not been approved in major markets like the USA, Europe, and India, the evidence from these studies is beyond the scope of this review.…”

Section: Efficacy Of Sglt2i 1 Dpp4i Fdcsmentioning

confidence: 99%

Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting

et al. 2022

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The Asian-Indian phenotype of type 2 diabetes mellitus is uniquely characterized for cardiometabolic risk. In the context of implementing patient-centric holistic cardio-metabolic risk management as a priority, the choice of various combinations of antidiabetic agents should be individualized. Combined therapy with two classes of antidiabetic agents, namely, dipeptidyl peptidase 4 inhibitors and sodiumglucose co-transporter-2 inhibitors, target several pathophysiological pathways. The wideranging clinical outcomes associated with this combination, including improvement of glycemia and adiposity, reduction of metabolic and vascular risk, safety, and simplicity for sustainable compliance, are extremely relevant to the Asian Indian patient population living with T2DM. In this review we describe the available evidence in detail and present a rational

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Section: Efficacy Of Sglt2i 1 Dpp4i Fdcsmentioning

confidence: 99%

Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting

et al. 2022

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“…Okahata et al reported that canagliflozin and canagliflozin/teneligliptin combination therapy improved blood glucose levels after MTT in 26 participants in a hospitalized setting for 6 days [19]. This study presented that canagliflozin increased that serum glucagon level during MTT and addition of teneligliptin reversed this increase.…”

Section: Discussionmentioning

confidence: 57%

Effect of Combination Therapy of Canagliflozin Added to Teneligliptin Monotherapy in Japanese Subjects with Type 2 Diabetes Mellitus: A Retrospective Study

Fushimi

Obata

Sanada

et al. 2020

Journal of Diabetes Research

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Recently, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors have been very often used in subjects with type 2 diabetes mellitus (T2DM). In addition, combination drugs of both inhibitors have attracted much attention in aspects of its cost-effectiveness and improvement of patients’ adherence. However, it is still poorly understood which factors are related to the efficacy of SGLT2 inhibitors as add-on therapy to DPP-4 inhibitors. Therefore, we aimed to elucidate in which type of individuals and/or under which conditions canagliflozin as add-on therapy to teneligliptin could exert more beneficial effects on glycemic control and/or renal protection. We retrospectively analyzed 56 Japanese subjects with T2DM in the real-world clinical practice. Three months after starting the combination therapy, the change of HbA1c (ΔHbA1c) was strongly related to HbA1c levels at baseline. As expected, serum glucagon level was increased after starting the combination therapy. Interestingly, however, the change of glucagon levels (Δglucagon) was not related to HbA1c levels at baseline, ΔHbA1c, and other parameters, which indicated that the increase of glucagon did not clinically affect the effectiveness of combination therapy. In addition, the change of urinary albumin excretion (ΔUAE) was negatively correlated with systolic blood pressure and HbA1c levels at baseline and positively correlated with the change of systolic blood pressure (ΔsBP) in univariate analysis. Furthermore, in multivariate analysis, only ΔsBP was the independent factor associated with ΔUAE. Taken together, canagliflozin as add-on therapy to teneligliptin improves glycemic control in a Δglucagon-independent manner and reduces UAE in a ΔsBP-dependent manner in Japanese subjects with T2DM.

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“…It has also been reported that glucagon secretion from alpha cells, in which no SGLT2 is expressed, of the pancreatic islets are suppressed via the SGLT1 inhibition effect [25]. However, some studies have reported increased glucagon levels with canagliflozin [26], further examination of There is a possibility that the metabolic cascade initiated from the energy deprivation followed by inhibiting renal reabsorption of glucose by SGLT2i extends to central nervous system (CNS) like "entero-insular-central axis", but no clinical data in this trial could elucidate this hypothesis, although ipragliflozin made some influence on leptin, which is known concerned with CNS [27].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive efficacy of ipragliflozin on various conditioned type 2 diabetes compared with dipeptidyl peptidase-4 inhibitors and with both agents, based on a real-world multicenter trial

et al. 2021

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Aims The effects of ipragliflozin, the first sodium-glucose co-transporter 2 inhibitors (SGLT2i) launched in Japan in 2014, and with dipeptidyl peptidase-4 inhibitors (DPP-4i) on glycemic control and metabolic changes were investigated comprehensively on various conditioned type 2 diabetes (T2DM) by evaluating various clinical parameters in a real-world setting. Materials and methods A total of 101 patients with T2DM aged 20-80 years with 7.0% ≤ HbA1c < 10.0% were followed in this 52-week, open-label, prospective, real-world, multicenter study. Results HbA1c decreased significantly in all groups. In ipragliflozin using groups, body weight, waist circumference, blood pressure, HOMA-IR, AST, ALT, γ-GTP, uric acid and leptin levels decreased, in contrast, HDL-cholesterol, total ketone bodies, blood urea nitrogen, creatinine, RBC, hemoglobin and hematocrit levels increased, however, in DPP-4i sole group, no significant trends were observed in these parameters. Change in leptin positively correlated with insulin, while change in total ketone bodies inversely correlated with ALT in ipragliflozin using groups. Fasting active gastric inhibitory polypeptide levels decreased in ipragliflozin sole group. Glucagon showed no changes. No significant safety concerns were observed in this study. Conclusions Ipragliflozin is useful and safe, showing some contrastive effects on several clinical parameters which are not shown with DPP-4i, resulting several clinical benefits. The co-administration of ipragliflozin and a DPP-4i has a better clinical outcome than either single-agent therapy. KeywordsDipeptidyl-peptidase-4 inhibitors • Ipragliflozin • Obese type 2 diabetes • Real-world multicenter clinical trial * Fumio Sawano

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Mechanistic insights from sequential combination therapy with a sodium glucose co‐transporter‐2 inhibitor and a dipeptidyl peptidase‐4 inhibitor: Results from the CANARIS Trial using canagliflozin and teneligliptin

Abstract: The result suggested that the dominant mechanism responsible for the glucose metabolism reflected in the G/I ratio was attributable to SGLT2i and that its active mechanism persisted, despite adding a DPP-4i.

Cited by 4 publications

References 22 publications

Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting

Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting

Effect of Combination Therapy of Canagliflozin Added to Teneligliptin Monotherapy in Japanese Subjects with Type 2 Diabetes Mellitus: A Retrospective Study

Comprehensive efficacy of ipragliflozin on various conditioned type 2 diabetes compared with dipeptidyl peptidase-4 inhibitors and with both agents, based on a real-world multicenter trial

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