Emerging therapeutic options in the management of diabetes: recent trends, challenges and future directions

Ansari, Mohammad Azam; Chauhan, Waseem; Shoaib, Shoaib; Alyahya, Sami A.; Ali, Mubashshir; Ashraf, Hamid; Alomary, Mohammad N.; Al-Suhaimi, Ebtesam A.

doi:10.1038/s41366-023-01369-3

Cited by 16 publications

(6 citation statements)

References 227 publications

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“…We assessed, while blinded to the results, study diagnostics to ensure reliability and generalizability for all comparisons and only report estimates that pass the diagnostics. 44,45 These study diagnostics included (1) minimum detectable risk ratio (MDRR) as a metric for statistical power, (2) preference score distributions between the target and comparator cohorts to evaluate empirical equipoise and population generalizability, and (3) cohort balance before and after propensity score (PS) adjustment, defined by the absolute SMDs on extensive patient characteristics. A study passed diagnostics if MDRR was less than 4, and >25% of patients had a preference score between 0•3 and 0•7 on both arms and maximum SMD <0•15 after PS adjustment.…”

Section: Discussionmentioning

confidence: 99%

“…Over the past decade, the therapeutic options for type 2 diabetes mellitus (T2DM) have undergone a significant transformation. 1,2 Sodium-glucose co-transporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) have expanded the role of antihyperglycemic agents from managing high blood glucose to addressing the elevated cardiovascular risk in patients with T2DM. [3][4][5][6] In several large randomized clinical trials (RCTs), SGLT2is and GLP1-RAs reduced major adverse cardiovascular events (MACE), such as myocardial infarction (MI), hospitalization for heart failure, and cardiovascular mortality.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Effectiveness of Second-line Antihyperglycemic Agents for Cardiovascular Outcomes: A Large-scale, Multinational, Federated Analysis of the LEGEND-T2DM Study

Khera,

Aminorroaya,

Dhingra

et al. 2024

Preprint

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BackgroundSGLT2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1-RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head trials.MethodsAcross the LEGEND-T2DM network, we included ten federated international data sources, spanning 1992-2021. We identified 1,492,855 patients with T2DM and established cardiovascular disease (CVD) on metformin monotherapy who initiated one of four second-line agents (SGLT2is, GLP1-RAs, dipeptidyl peptidase 4 inhibitor [DPP4is], sulfonylureas [SUs]). We used large-scale propensity score models to conduct an active comparator, target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, we fit on-treatment Cox proportional hazard models for 3-point MACE (myocardial infarction, stroke, death) and 4-point MACE (3-point MACE + heart failure hospitalization) risk, and combined hazard ratio (HR) estimates in a random-effects meta-analysis.FindingsAcross cohorts, 16·4%, 8·3%, 27·7%, and 47·6% of individuals with T2DM initiated SGLT2is, GLP1-RAs, DPP4is, and SUs, respectively. Over 5·2 million patient-years of follow-up and 489 million patient-days of time at-risk, there were 25,982 3-point MACE and 41,447 4-point MACE events. SGLT2is and GLP1-RAs were associated with a lower risk for 3-point MACE compared with DPP4is (HR 0·89 [95% CI, 0·79-1·00] and 0·83 [0·70-0·98]), and SUs (HR 0·76 [0·65-0·89] and 0·71 [0·59-0·86]). DPP4is were associated with a lower 3-point MACE risk versus SUs (HR 0·87 [0·79-0·95]). The pattern was consistent for 4-point MACE for the comparisons above. There were no significant differences between SGLT2is and GLP1-RAs for 3-point or 4-point MACE (HR 1·06 [0·96-1·17] and 1·05 [0·97-1·13]).InterpretationIn patients with T2DM and established CVD, we found comparable cardiovascular risk reduction with SGLT2is and GLP1-RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of GLP1-RAs and SGLT2is should be prioritized as second-line agents in those with established CVD.FundingNational Institutes of Health, United States Department of Veterans Affairs

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative Effectiveness of Second-line Antihyperglycemic Agents for Cardiovascular Outcomes: A Large-scale, Multinational, Federated Analysis of the LEGEND-T2DM Study

Khera,

Aminorroaya,

Dhingra

et al. 2024

Preprint

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“…Herbal medicines stimulate incretin secretion in mice[ 27 , 28 ]. In that study, TJ-43 did not affect postprandial glucose, active GLP-1, triglyceride, or remnant-like particle cholesterol responses[ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Rikkunshito increases peripheral incretin-hormone levels in humans and rats

Kono,

Furuya,

Akaike

et al. 2024

World J Methodol

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BACKGROUND It was reported that rikkunshito (TJ-43) improved the cisplatin-induced decreases in the active form of ghrelin in plasma; however, other effects on gastrointestinal hormones have not been investigated. AIM To investigate the effects of TJ-43 on peripheral levels of incretin hormones, including gastric inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1), in humans and rats. METHODS Patients were divided into two groups, namely patients who received TJ-43 immediately following surgery [TJ-43(+) group] and those who received TJ-43 on postoperative day 21 [TJ-43(-) group], and the plasma levels of active GIP and active GLP-1 were assessed. In animal experiments, rats were treated with TJ-43 [rat (r)TJ-43(+) group] or without [rTJ-43(−) group] by gavage for 4 wk, and the plasma active GIP and active GLP-1 levels were measured. The expression of incretin hormones in the gastrointestinal tract and insulin in the pancreas were investigated by immunohistochemistry. Furthermore, the cyclic adenosine monophosphate activities were assessed in pancreatic tissues from rats treated with or without TJ-43 in vivo , and the blood glucose levels and plasma insulin levels were measured in rats treated with or without TJ-43 in oral glucose tolerance tests. RESULTS In humans, the active incretin hormone levels increased, and values were significantly greater in the TJ-43(+) group compared those in the TJ-43(-) group. In rats, the plasma active incretin levels significantly increased in the rTJ-43(+) group compared with those in the rTJ-43(-) group. GIP and GLP-1 expressions were enhanced by TJ-43 treatment. Moreover, plasma insulin levels increased and blood glucose levels were blunted in the rTJ-43(+) group. CONCLUSION The results show that TJ-43 may be beneficial for patients who undergo pancreatic surgery.

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“…Citrus medica essential oil also showed anti-diabetic and hypoglycemic activity in in vivo studies [ 237 ]. This activity was related to the phytochemicals that are present in peel oil, which might facilitate access to the enzymatic site [ 238 , 239 ].…”

Section: Physiological Threatsmentioning

confidence: 99%

Unveiling the Chemistry of Citrus Peel: Insights into Nutraceutical Potential and Therapeutic Applications

Munir,

Yaqoob,

Awan

et al. 2024

Foods

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The recent millennium has witnessed a notable shift in consumer focus towards natural products for addressing lifestyle-related disorders, driven by their safety and cost-effectiveness. Nutraceuticals and functional foods play an imperative role by meeting nutritional needs and offering medicinal benefits. With increased scientific knowledge and awareness, the significance of a healthy lifestyle, including diet, in reducing disease risk is widely acknowledged, facilitating access to a diverse and safer diet for longevity. Plant-based foods rich in phytochemicals are increasingly popular and effectively utilized in disease management. Agricultural waste from plant-based foods is being recognized as a valuable source of nutraceuticals for dietary interventions. Citrus peels, known for their diverse flavonoids, are emerging as a promising health-promoting ingredient. Globally, citrus production yields approximately 15 million tons of by-products annually, highlighting the substantial potential for utilizing citrus waste in phyto-therapeutic and nutraceutical applications. Citrus peels are a rich source of flavonoids, with concentrations ranging from 2.5 to 5.5 g/100 g dry weight, depending on the citrus variety. The most abundant flavonoids in citrus peel include hesperidin and naringin, as well as essential oils rich in monoterpenes like limonene. The peel extracts exhibit high antioxidant capacity, with DPPH radical scavenging activities ranging from 70 to 90%, comparable to synthetic antioxidants like BHA and BHT. Additionally, the flavonoids present in citrus peel have been found to have antioxidant properties, which can help reduce oxidative stress by 30% and cardiovascular disease by 25%. Potent anti-inflammatory effects have also been demonstrated, reducing inflammatory markers such as IL-6 and TNF-α by up to 40% in cell culture studies. These findings highlight the potential of citrus peel as a valuable source of nutraceuticals in diet-based therapies.

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Emerging therapeutic options in the management of diabetes: recent trends, challenges and future directions

Cited by 16 publications

References 227 publications

Comparative Effectiveness of Second-line Antihyperglycemic Agents for Cardiovascular Outcomes: A Large-scale, Multinational, Federated Analysis of the LEGEND-T2DM Study

Comparative Effectiveness of Second-line Antihyperglycemic Agents for Cardiovascular Outcomes: A Large-scale, Multinational, Federated Analysis of the LEGEND-T2DM Study

Rikkunshito increases peripheral incretin-hormone levels in humans and rats

Unveiling the Chemistry of Citrus Peel: Insights into Nutraceutical Potential and Therapeutic Applications

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