scholarly journals High-Dose Liraglutide and SGLT2 Inhibitor: A Promising Combination

2021 ◽  
Vol 12 (1) ◽  
pp. 1-7
Author(s):  
Marvin Wei Jie Chua
Keyword(s):  
Combination Therapy ◽  
Metabolic Diseases ◽  
Sglt2 Inhibitor ◽  
High Dose ◽  
Clinical Effects ◽  
Rapid Improvement ◽  
Glucose Lowering ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists are important drugs in our armamentarium of treatment for Type 2 diabetes mellitus (DM). In addition to their glucose-lowering effects, they have effects on weight, other metabolic diseases and perhaps most importantly, a cardioprotective and reno-protective effect. Liraglutide is a long-acting GLP-1 agonist which was originally used at 1.8 mg daily for the treatment of DM. However, high-dose liraglutide—liraglutide 3 mg daily, has been demonstrated to be a safe and effective treatment for obesity, with or without DM. In this manuscript, I present two patients who had unusual responses to combination therapy with high-dose liraglutide and SGLT2 inhibitor—marked and/or rapid improvement in glycemic control and weight loss. Drawing from the observations in both cases, I discuss the complementary mechanisms of actions of both drugs, review the clinical effects of combination therapy and distil them into clinical pearls of practical utility for the physician. Given the “clash of the two pandemics” of obesity and COVID-19 and the burgeoning rates of obesity which loom in the near horizon, this is most timely.

scholarly journals Combination Therapy with an SGLT2 Inhibitor as Initial Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 8 (1) ◽  
pp. 45 ◽  
Author(s):  
Tamara Y. Milder ◽  
Sophie L. Stocker ◽  
Christina Abdel Shaheed ◽  
Lucy McGrath-Cadell ◽  
Dorit Samocha-Bonet ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Low Dose ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Cochrane Library ◽  
High Dose ◽  
Dose Combination ◽  
Inhibitor Combination

Background: Guidelines differ with regard to indications for initial combination pharmacotherapy for type 2 diabetes. Aims: To compare the efficacy and safety of (i) sodium-glucose cotransporter 2 (SGLT2) inhibitor combination therapy in treatment-naïve type 2 diabetes adults; (ii) initial high and low dose SGLT2 inhibitor combination therapy. Methods: PubMed, Embase and Cochrane Library were searched for randomised controlled trials (RCTs) of initial SGLT2 combination therapy. Mean difference (MD) for changes from baseline (HbA1c, weight, blood pressure) after 24–26 weeks of treatment and relative risks (RR, safety) were calculated using a random-effects model. Risk of bias and quality of evidence was assessed. Results: In 4 RCTs (n = 3749) there was moderate quality evidence that SGLT2 inhibitor/metformin combination therapy resulted in a greater reduction in HbA1c (MD (95% CI); −0.55% (−0.67, −0.43)) and weight (−2.00 kg (−2.34, −1.66)) compared with metformin monotherapy, and a greater reduction in HbA1c (−0.59% (−0.72, −0.46)) and weight (−0.57 kg (−0.89, −0.25)) compared with SGLT2 inhibitor monotherapy. The high dose SGLT2 inhibitor/metformin combination resulted in a similar HbA1c but greater weight reduction; −0.47 kg (−0.88, −0.06) than the low dose combination therapy. The RR of genital infection with combination therapy was 2.22 (95% CI 1.33, 3.72) and 0.69 (95% CI 0.50, 0.96) compared with metformin and SGLT2 inhibitor monotherapy, respectively. The RR of diarrhoea was 2.23 (95% CI 1.46, 3.40) with combination therapy compared with SGLT2 inhibitor monotherapy. Conclusions: Initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy.

scholarly journals How glucagon-like peptide 1 receptor agonists work

2021 ◽  
Author(s):  
Christine Rode Andreasen ◽  
Andreas Andersen ◽  
Filip Krag Knop ◽  
Tina Vilsbøll
Keyword(s):  
Body Weight ◽  
Therapeutic Potential ◽  
Clinical Effects ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Reduce Body Weight ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Clinical Utilisation

Recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of actions, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

scholarly journals From glucose lowering agents to disease/diabetes modifying drugs: a “SIMPLE” approach for the treatment of type 2 diabetes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ofri Mosenzon ◽  
Stefano Del Prato ◽  
Meir Schechter ◽  
Lawrence A. Leiter ◽  
Antonio Ceriello ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Primary Care ◽  
Combination Therapy ◽  
Simple Approach ◽  
Glucose Lowering ◽  
Disease Modifying Drugs ◽  
Safe Side ◽  
Glucagon Like Peptide 1 ◽  
Early Combination Therapy

AbstractDuring the last decade we experienced a surge in the number of glucose lowering agents that can be used to treat patients with type 2 diabetes. Especially important are the discoveries that sodium glucose co-transporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve patients’ cardiovascular and renal outcomes. Accordingly, various medical associations have updated their guidelines for the treatment of diabetes in this new era. Though not agreeing on every issue, these position-statements generally share a detailed and often complex workflow that may be too complicated for the busy and overworked primary care setting, where the majority of patients with type 2 diabetes are managed in many countries. Other guidelines, generally those from the cardiology associations focus primarily on the population of patients with high risk for or pre-existing cardiovascular disease, which represent only the minority of patients with type 2 diabetes. We believe that we should re-define SGLT2i and GLP-1 RA as diabetes/disease modifying drugs (DMDs) given the recent evidence of their cardiovascular and renal benefits. Based on this definition we have designed a SIMPLE approach in order to assist primary care teams in selecting the most appropriate therapy for their patients. We believe that most subjects newly diagnosed with type 2 diabetes should initiate early combination therapy with metformin and a prognosis changing DMD. The decision whether to use GLP-1 RA or SGLT2i should be made based on specific patient’s risk factors and preferences. Importantly, DMDs are known to have a generally safe side-effect profile, with lower risk for hypoglycemia and weight gain, further promoting their wider usage. Early combination therapy with DMDs may improve the multiple pathophysiological abnormalities responsible for type 2 diabetes and its complications, thus resulting in the greatest long term benefits.

Glucagon-like peptide-1 loaded phospholipid micelles for the treatment of type 2 diabetes: improved pharmacokinetic behaviours and prolonged glucose-lowering effects

RSC Advances ◽  
2016 ◽  
Vol 6 (97) ◽  
pp. 94408-94416 ◽  
Author(s):  
Xu Cui ◽  
Qinghua Meng ◽  
Yingying Chu ◽  
Xiaoke Gu ◽  
Yan Tang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hypoglycemic Activity ◽  
Glucose Lowering ◽  
Phospholipid Micelles ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

GLP-1-SSM, a sterically stabilized GLP-1 in phospholipid micelles, exhibited improved hypoglycemic activity and long-acting antidiabetic ability.

Efficacy of dapagliflozin in combination therapy with the glucagon-like peptide-1 analog in obese patients with type 2 diabetes

2015 ◽  
Vol 2 (e1) ◽  
pp. 008-008
Author(s):  
Momoko Isono ◽  
Kazuya Fujihara ◽  
Shoko Furukawa ◽  
Ryo Kumagai ◽  
Hiroaki Yagyu
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Obese Patients ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects

2021 ◽  
Vol 22 (11) ◽  
pp. 5863
Author(s):  
Giuseppe Palmiero ◽  
Arturo Cesaro ◽  
Erica Vetrano ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Transporter ◽  
The Elderly ◽  
Intracellular Sodium ◽  
Clinical Effects ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Transporter 2 ◽  
Function Impairment

Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients’ exposure to gliflozins’ treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events.

The Use of SGLT2i and GLP-1 RA in Patients with Type 2 Diabetes in Thailand: Evidence Review and Recommendations

2021 ◽  
Vol 104 (11) ◽  
pp. 1850-1865
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Lowering ◽  
Sodium Glucose Cotransporter ◽  
Evidence Review ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Lowering Therapy ◽  
The Cost ◽  
Selection Of

Background: Cardiovascular (CV) and renal comorbidities are common among type 2 diabetes (T2D) patients, and significantly increase the cost and burden of care. Both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve key outcomes including major CV events, hospitalization for heart failure, and renal outcomes, albeit to varying degrees in different T2D populations. Materials and Methods: The authors reviewed evidence from GLP-1 RA and SGLT2i CV outcomes trials and real-world studies in Thailand and elsewhere. Results: The authors formulated recommendations to guide selection of anti-diabetes medication based on patients’ clinical characteristics and CV or renal risk profile. Conclusion: These recommendations could help guide management of CV/renal comorbidities and risk alongside glucose-lowering therapy for individual patients. Keywords: Type 2 diabetes mellitus; Cardiovascular diseases; Chronic kidney disease; Clinical outcomes; SGLT2i; GLP-1 RA

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