Glucose Lowering In Type Research Articles

FRI649 ADMIRE: Assessing Dapagliflozin And Metformin As An Initial Regimen In Diabetes Mellitus For Enhanced Glucose Control

Abstract Disclosure: D. Phadke: None. D. Gopal: None. D. Biswas: None. D. Birla: None. A. Prasad: None. P. Joshi: None. Introduction: Early aggressive glucose lowering in type 2 diabetes mellitus (T2DM) has shown improved outcomes, and combination oral antidiabetic agents (OAAs) on top of lifestyle therapy are necessary. In India, most T2DM patients receive combination therapy with two or more OAAs to achieve glycemic targets more rapidly. The fixed dose combination (FDC) of dapagliflozin and metformin is widely used in India, as it improves glycemia, reduces weight and blood pressure (BP), and has good tolerability. This study aimed to evaluate physician practices, efficacy, and tolerability of dapagliflozin and metformin FDC as initial therapy for T2DM patients in a real-world setting. Methods: This multicenter, retrospective, observational study enrolled 481 T2DM patients across 49 clinical units for a period of 6 months. The study aimed to evaluate physician practices, efficacy, and tolerability of dapagliflozin and metformin FDC as the initial choice FDC in T2DM. The study was conducted in compliance with the principles of the Declaration of Helsinki, good clinical practice, and regulatory guidelines. Ethical approval for the study was obtained on August 6, 2022, and the study was conducted from August 15, 2022, to January 20, 2023. Results: The study demonstrated that dapagliflozin and metformin FDC significantly reduced weight by 4.2 kg (p < 0.0001), fasting plasma glucose by 21.4 mg/dL (p < 0.0001), and improved estimated glomerular filtration rate (eGFR) by 1.9 m²/1.73 ml/min (p < 0.0001). Additionally, systolic BP was reduced by 10.7 mmHg (p < 0.0001), and diastolic BP was reduced by 6.6 mmHg (p < 0.0001), which is in combination with the concomitant medications. Incidence of genito-urinary tract infection was 8.9%. Conclusion: In a real-world setting, dapagliflozin and metformin FDC can be used as initial therapy for T2DM with good efficacy, tolerability, and safety. Physicians preferred this combination due to its ability to promote weight loss, reduce cardiovascular events, and decline in renal function. The excellent safety and efficacy reported by physicians for this FDC of dapagliflozin and metformin has contributed to improved compliance with the treatment. Thus, in the Indian population, dapagliflozin and metformin FDC is effective, safe, and has good tolerability as an initial therapy for T2DM. Presentation: Friday, June 16, 2023

Does a Supplement Cocktail a Day Keep the Doctor Away? An Unusual Case of Alcohol Induced Diabetes Mellitus: A Case Report and Review of Literature

Background: Currently there are no evidence-based medical recommendations to support the use of supplements in type 1 diabetes mellitus (DM), although there is some data that supports glucose lowering in type 2 DM with supplements such as cinnamon. Additionally, there is no evidence regarding the use of supplements in insulin-dependent DM secondary to pancreatic dysfunction from alcohol use disorder. Despite lack of clear evidence, it is estimated that more than 65% of Americans with DM use at least one dietary supplement for perceived health benefits. (1)Clinical Case: A 58-year old male presented with insulin-dependent DM secondary to pancreatic dysfunction from alcohol use disorder. Initial labs were significant for a low C-peptide of 0.13 ng/mL (0.80–3.85 ng/mL), A1c -9.4%, and blood glucoses ranging from 160–300 mg/dL. Patient’s DM regimen consisted of glargine 40 units nightly and aspart 12 units three times a day with meals. On a subsequent visit two months later, the patient stated that he had begun taking numerous supplements in hopes that these would improve his overall medical status. Supplements included Blood Boost Formula, Ultra K2 with MK-7, Chromium Picolinate, Male Enhancement, Super C Immune Complex, Nugenix Total-T, Niacinamide, Omega Q Plus Max, Cortisol Hormone Balancer, and Vitamin D3. Simultaneously, the patient self-discontinued all his maintenance medications except for his aforementioned insulin regimen due to the fear of negatively impacting his pancreas. Unexpectedly, his blood glucoses improved to a range of 90–150 mg/dL after being on these supplements without increasing his insulin dose. Upon literature review, three ingredients showed the most evidence for the possible explanation for his improvement in glucose control: L-arginine, nettle extract, and biotin with chromium. Conclusion: Literature review of in vivo and randomized, placebo-controlled studies demonstrated mechanisms of action for L-arginine, nettle extract, and biotin with chromium that indicate their potential role in lowering blood glucoses and increasing C-peptide levels in insulin-dependent DM secondary to pancreatic dysfunction from alcohol use disorder. Further investigations include exploring long-term impact on pancreatic function, glucose control, and insulin resistance. Reference: (1) Garrow, D., Egede, L. Association Between Complementary and Alternative Medicine Use, Preventive Care Practices, and Use of Conventional Medical Services Among Adults with Diabetes. Diabetes Care 2006 Jan; 29(1): 15–19.

Beinaglutide shows significantly beneficial effects in diabetes/obesity-induced nonalcoholic steatohepatitis in ob/ob mouse model

AimsBeinaglutide has been approved for glucose lowering in type 2 diabetes mellitus (T2DM) in China. In addition to glycemic control, significant weight loss is observed from real world data. This study is designed to investigate the pharmacological and pharmacokinetic profiles of beinaglutide in different models. MethodsThe pharmacological efficacy of beinaglutide was evaluated in C57BL/6 and ob/ob mice after single administration. Pharmacokinetic profiles in mice were investigated after single or multiple administration. Sub-chronic pharmacological efficacy was investigated in ob/ob mice for two weeks treatment and diet-induced ob/ob mice model of nonalcoholic steatohepatitis (NASH) for four weeks treatment. Key findingsBeinaglutide could dose-dependently reduce the glucose levels and improve insulin secretion in glucose tolerance tests, inhibit food intake and gastric emptying after single administration. At higher doses, beinaglutide could inhibit food intake over 4 h, which results in weight loss in ob/ob mice after about two weeks treatment. No tachyphylaxis is observed for beinaglutide in food intake with repeated administration. In NASH model, beinaglutide could reduce liver weight and hepatic steatosis and improve insulin sensitivity. Signiant changes of gene levels were observed in fatty acid β-oxidation (Ppara, Acadl, Acox1), mitochondrial function (Mfn1, Mfn2), antioxidation (Sod2), Sirt1, and et al. SignificanceOur results characterize the pharmacological and pharmacokinetic profiles of beinaglutide in mice and supported that chronic use of beinaglutde could lead to weight loss and reduce hepatic steatosis, which suggest beinaglutide may be effective therapy for the treatment of obesity and NASH.

Cardiovascular, renal and liver protection with novel antidiabetic agents beyond blood glucose lowering in type 2 diabetes: consensus article from the European Society of Hypertension Working Group on Obesity, Diabetes and the High-risk Patient.

: The prevalence of type 2 diabetes (T2D) has increased over the past few decades. T2D has a strong genetic propensity that becomes overt when a patient is exposed to a typical Western lifestyle, gain weight and becomes obese, whereas weight loss protects from the development of T2D. Except of lifestyle modifications, the choice of the appropriate treatment is essential in the management of patients with T2D and appears critical for the obese population with T2D. The new pharmacological approach for the treatment of T2D, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, seems to be effective not only in the management of T2D but also for weight loss, reduction of blood pressure and improvement of nonalcoholic fatty liver disease. Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 analogues reduced cardiovascular risk, prevented cardiovascular disease and mortality, thereby playing an important role in the treatment of obese patients with hypertension and T2D.

Sodium-glucose cotransporter 2 inhibition: towards an indication to treat diabetic kidney disease.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have clearly demonstrated their beneficial effect in diabetic kidney disease (DKD) on top of the standard of care [blood glucose control, renin–angiotensin system blockade, smoking cessation and blood pressure (BP) control], even in patients with overt DKD. However, the indication of this drug class is still blood glucose lowering in type 2 diabetic patients with estimated glomerular filtration rate >45 mL/min/1.73 m2. Based on the new evidence, several scientific societies have emphasized the preferential prescription of SGLT2i for patients at risk of heart failure or kidney disease, but still within the limits set by health authorities. A rapid positioning of both the European Medicines Agency and the US Food and Drug Administration will allow patients with overt DKD to benefit from SGLT2i. Clinical experience suggests that SGLT2i safety management may in part mirror renin–angiotensin blockade safety management in patients with overt DKD. This review focuses on the rationale for an indication of SGTL2i in DKD. We further propose clinical steps for maximizing the safety of SGLT2i in DKD patients on other antidiabetic, BP or diuretic medication.

Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function.

Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease, including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 in whom the drug is not currently approved for use. The CANVAS Program randomized 10 142 participants with type 2 diabetes and eGFR >30 mL/min/1.73 m2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without chronic kidney disease, defined as eGFR <60 and ≥60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45, 45 to <60, 60 to <90, and ≥90 mL/min/1.73 m2). At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m2, 71.6% of whom had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55-0.90) and those with preserved kidney function (hazard ratio, 0.92; 95% CI, 0.79-1.07; P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity = 0.01), as were results for almost all safety outcomes. The effects of canagliflozin on cardiovascular and renal outcomes were not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m2. Reassessing current limitations on the use of canagliflozin in chronic kidney disease may allow additional individuals to benefit from this therapy. URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629, NCT01989754.

Canagliflozin and Cardiovascular (CV) Outcomes in Patients with Chronic Kidney Disease

SGLT2 inhibitors are approved for glucose lowering in type 2 diabetes (T2DM) and have proven CV benefits, but are not approved for people with significantly reduced kidney function as glycemic efficacy is dependent on glomerular filtration. This analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program assessed effects of canagliflozin on CV outcomes in T2DM according to kidney function (estimated glomerular filtration rate [eGFR] &amp;lt;45, 45-&amp;lt;60, 60-&amp;lt;90, and ≥90 ml/min/1.73 m2). The CANVAS Program included 2039 patients (20.1%) with baseline eGFR &amp;lt;60 ml/min/1.73 m2 (mean age 68 y, BP 138/76 mmHg, HbA1c 8.3%, eGFR 49 ml/min/1.73 m2, median urinary albumin:creatinine ratio 22 mg/g). Effects of canagliflozin on HbA1c and body weight were smaller in patients with eGFR &amp;lt;60 vs. ≥60; ml/min/1.73 m2 (-0.43 vs. -0.64%, P-heterogeneity &amp;lt;0.0001, and -1.16 vs. -1.43 kg, P-heterogeneity = 0.0002), but BP effects were similar (-3.89 vs. -4.11 mmHg, P-heterogeneity = 0.21). Relative effects on the primary and most other CV outcomes were similar across four eGFR subgroups, with possible heterogeneity suggested only for the exploratory outcome of stroke (Figure). Results for almost all safety outcomes were also consistent across eGFR subgroups. Despite smaller glycemic effects in people with reduced eGFR, the cardioprotective benefits of canagliflozin are similar across different levels of kidney function. Disclosure B.L. Neuen: Employee; Self; The George Institute for Global Health. T. Ohkuma: None. B. Neal: Research Support; Self; Australian National Health and Medical Research Council Principal Research Fellowship. Other Relationship; Self; Janssen Scientific Affairs, LLC., Roche Pharma, Servier. Research Support; Self; Merck Schering Plough. Advisory Panel; Self; Abbott, Novartis Pharmaceuticals Corporation, Pfizer Inc. D.R. Matthews: Other Relationship; Self; Janssen Scientific Affairs, LLC., Novo Nordisk Inc., GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Eli Lilly and Company, Sanofi-Aventis, Servier, Aché Laboratories. D. de Zeeuw: Other Relationship; Self; AbbVie Inc., Astellas Pharma US, Inc., Eli Lilly and Company, Fresenius SE &amp; Co. KGaA, Janssen Scientific Affairs, LLC., Boehringer Ingelheim GmbH, Bayer AG, Mitsubishi Tanabe Pharma Corporation. K.W. Mahaffey: Research Support; Self; Afferent, Amgen, AstraZeneca, Daiichi, Ferring, Google (Verily), Janssen, Medtronic, Merck, Novartis, Sanofi, and St. Jude. Consultant; Self; Ablynx, AstraZeneca, BAROnova, Bio2 Medical, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiometabolic Health Congress, Cubist, Eli Lilly, Elsevier, Epson, GlaxoSmithKline, Janssen, Merck, Mt. Sinai, Radiometer, Springer Publishing, The Medicines Company, Theravance, Vindico, and WebMD. Stock/Shareholder; Self; BioPrint Fitness. G. Fulcher: Other Relationship; Self; Novo Nordisk Inc., Janssen Scientific Affairs, LLC., Boehringer Ingelheim GmbH, Merck Sharp &amp; Dohme Corp. M. Desai: Employee; Self; Janssen Research&amp;Development. Q. Li: Employee; Self; George Institute for Global Health. H. Deng: Employee; Self; Janssen Research&amp;Development. N. Rosenthal: Employee; Self; Janssen Research &amp; Development. M. Jardine: Other Relationship; Self; Fellowships. Research Support; Self; Gambro, Baxter, CSL Behring, Amgen Inc., Eli Lilly and Company, Merck &amp; Co., Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Baxter, Amgen Inc., Roche Pharma. G. Bakris: Other Relationship; Self; Forest Labs, Takeda, Medtronic (15%), Relypsa (15%). Consultant; Self; Takeda, Abbott, CVRx, Johnson&amp;Johnson, Eli Lilly, Food and Drug Administration. Board Member; Self; National Kidney Foundation, American Society of Hypertension. Other Relationship; Self; Editor-Am J Nephrology, HTN ed. UpToDate, Assoc. Ed.- Diabetes Care, Nephrology Dialysis and Transpl. V. Perkovic: Research Support; Self; Australian National Health and Medical Research Council (Senior Research Fellowship and Program Grant). Other Relationship; Self; AbbVie, Boehringer Ingelheim, GlaxoSmithKline, Janssen, and Pfizer. Advisory Panel; Self; AbbVie, Astellas, AstraZeneca, Bayer, Baxter, Bristol-Myers Squibb, Boehringer Ingelheim, Durect, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relyps.

Cardiovascular Protection in People With Diabetes.

Cardiovascular Protection in People With Diabetes.

Advanced Glycation End Products, Oxidation Products, and Incident Cardiovascular Events in Patients With Type 2 Diabetes.

OBJECTIVEThe goal of this study was to determine whether plasma levels of advanced glycation end products (AGE) and oxidation products (OP) predict the incidence of cardiovascular disease (CVD) in type 2 diabetes.RESEARCH DESIGN AND METHODSFive specific AGE (methylglyoxal hydroimidazolone, carboxymethyl lysine, carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone, and glyoxal hydroimidazolone) and two OP (2-aminoadipic acid and methionine sulfoxide [MetSO]) were measured at baseline in two intensive glucose-lowering studies: 1) a subcohort of the Veterans Affairs Diabetes Trial (VADT) (n = 445) and 2) a nested case-control subgroup from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (n = 271).RESULTSIncreased levels of several AGE and OP were associated with older age, decreased kidney function, previous CVD, and longer diabetes duration, but not with hemoglobin A1c. In the VADT, increased risk of incident CVD events (n = 107) was associated with lower MetSO after adjusting for age, race/ethnicity, sex, prior CVD event, kidney function, treatment assignment, and diabetes duration (hazard ratio [HR] 0.53; 95% CI 0.28–0.99; P = 0.047). Individuals with both low MetSO and high 3-deoxyglucosone hydroimidazolone concentrations were at highest risk for CVD (HR 1.70; P = 0.01). In the ACCORD study, those with incident CVD events (n = 136) had lower MetSO (by 14%; P = 0.007) and higher glyoxal hydroimidazolone and carboxymethyl lysine (by 18% and 15%, respectively; P = 0.04 for both); however, only the difference in MetSO remained significant after adjustment for prior CVD event (P = 0.002).CONCLUSIONSLower levels of MetSO and higher levels of select AGE are associated with increased incident CVD and may help account for the limited benefit of intensive glucose lowering in type 2 diabetes.

Antidiabetic Effects of Vigna nakashimae Extract in Humans: A Preliminary Study.

Vigna nakashimae (VN) extract has been shown to have antidiabetic and antiobesity effects in various animal studies; however, to our knowledge, no data on such effects exist in humans. We performed a randomized placebo-controlled study to investigate the antidiabetic effects of VN extract treatment for 12 weeks in humans. A total of 18 Korean patients with type 2 diabetes were enrolled in this study and were allocated randomly to either the VN extract group (1 g thrice daily) or control group (placebo tablets) for 12 weeks. We investigated blood glucose levels, body weight, lipid profiles, and adverse events after 12 weeks of treatment. Fifteen subjects were included in the final analysis. There was no difference in age, sex, fasting glucose levels, or lipid profiles between the VN extract and control groups at baseline. However, the baseline glycosylated hemoglobin (HbA1c) levels of the control group were lower than those of the VN extract group. After treatment with VN extract for 12 weeks, the body weight and lipid profile of the VN extract group remained unchanged; however, the HbA1C levels decreased by 0.36% ± 0.33% (p = 0.027). In contrast, the HbA1C levels of the control group did not change after 12 weeks (p = 0.228). During the 12-week treatment with VN extract, no serious adverse events were reported. Our data indicate that VN extract has implications for glucose lowering in type 2 diabetic patients.

GPR120 suppresses adipose tissue lipolysis and synergizes with GPR40 in antidiabetic efficacy

GPR40 and GPR120 are fatty acid sensors that play important roles in glucose and energy homeostasis. GPR40 potentiates glucose-dependent insulin secretion and demonstrated in clinical studies robust glucose lowering in type 2 diabetes. GPR120 improves insulin sensitivity in rodents, albeit its mechanism of action is not fully understood. Here, we postulated that the antidiabetic efficacy of GPR40 could be enhanced by coactivating GPR120. A combination of GPR40 and GPR120 agonists in db/db mice, as well as a single molecule with dual agonist activities, achieved superior glycemic control compared with either monotherapy. Compared with a GPR40 selective agonist, the dual agonist improved insulin sensitivity in ob/ob mice measured by hyperinsulinemic-euglycemic clamp, preserved islet morphology, and increased expression of several key lipolytic genes in adipose tissue of Zucker diabetic fatty rats. Novel insights into the mechanism of action for GPR120 were obtained. Selective GPR120 activation suppressed lipolysis in primary white adipocytes, although this effect was attenuated in adipocytes from obese rats and obese rhesus, and sensitized the antilipolytic effect of insulin in rat and rhesus primary adipocytes. In conclusion, GPR120 agonism enhances insulin action in adipose tissue and yields a synergistic efficacy when combined with GPR40 agonism.

P5354Relationship between outcome reductions and the extent of glucose lowering in type 2 diabetes mellitus: meta-regression analysis of randomized trials

P5354Relationship between outcome reductions and the extent of glucose lowering in type 2 diabetes mellitus: meta-regression analysis of randomized trials

Intensive glucose-lowering in type 2 diabetes was linked to hypoglycemia in high-complexity patients.

Source Citation McCoy RG, Lipska KJ, Yao X, et al. Intensive treatment and severe hypoglycemia among adults with type 2 diabetes. JAMA Intern Med. 2016; 176:969-78. 27273792

Insulin therapy in insulin resistance: Could it be part of a lethal pathway?

Insulin therapy in insulin resistance: Could it be part of a lethal pathway?

The glucagon‐like peptide‐1 receptor antagonist exendin‐9 elevates blood pressure and worsens renal function in SHR (1136.18)

Pharmacological administration of glucagon‐like peptide‐1 receptor (GLP‐1R) agonists exert cardiorenal beneficial effects beyond blood glucose lowering in type II diabetes and non‐diabetic patients, including reduction of blood pressure. The present study aimed to test the hypothesis that baseline levels of GLP‐1R signaling play a role on blood pressure regulation in hypertensive rats. To this end, 5‐week‐old SHRs were treated with the GLP‐1R antagonist exendin‐9 (EX‐9; 10 µg/rat/day), the GLP‐1R agonist exendin‐4 (EX‐4; 2.5 µg/rat/day) or saline (control) via osmotic mini‐pumps during 4 weeks. Direct recording of BP at the end of the treatment demonstrated that mean blood pressure (MBP) was elevated by exendin‐9 treatment (182±4 mmHg) and lowered by exendin‐4 treatment (161±4 mmHg) when compared to controls (172±1 mmHg, all P&lt;0.05). Exendin‐9 treated SHR also exhibited significantly elevated proteinuria, renal fibrosis, renal TGF‐beta and angiotensinogen expression and macrophage infiltration versus controls. Conversely, exendin‐4 administration exerted anti‐proteinuric, anti‐fibrotic and anti‐inflammatory effects. These findings support the hypothesis that endogenous GLP‐1 levels exert blood pressure lowering and renoprotective effects in hypertensive rats.Grant Funding Source: Supported by FAPESP and USC.

Preventable Coronary Heart Disease Events from Control of Cardiovascular Risk Factors in US Adults With Diabetes (Projections from Utilizing the UKPDS Risk Engine)

Type 2 diabetes mellitus (T2DM) carries significant risks for coronary heart disease (CHD). We examined the potential US population impact of single and composite risk factor control. Among US adults with diagnosed T2DM aged≥30 years in the National Health and Nutrition Examination Survey 2007 to 2012, we assessed CHD events preventable using the United Kingdom Prospective Diabetes Study CHD risk engine. We examined in all those not at goal the impact of statistical control of smoking, glycated hemoglobin, systolic blood pressure, and total and high-density lipoprotein cholesterol, according to the predefined criteria setting risk factors at different levels of control representing (1) "All to Goal," (2) at "Nominal Control," or (3) at "Aggressive Control." Preventable CHD events represented the difference between the number of events estimated from the control of these risk factors versus current levels of the risk factors. Of 606 men (representing 6.2 million) and 603 women (6.3 million) with DM and no previous CHD, 1.3 million men and 0.7 million women would develop a CHD event within 10 years if left uncontrolled. Controlling all risk factors to goal was projected to prevent 35% and 45% of CHD events in men and women, respectively. Nominal risk factor control was projected to prevent 36% and 38% and aggressive control 51% and 61% of CHD events, respectively. In conclusion, a significant proportion of CHD events in adults with T2DM could be prevented from composite control of risk factors often not at goal.

Combined antidiabetic benefits of exenatide and dapagliflozin in diabetic mice

The combined glucose-lowering effect of exenatide and dapagliflozin has not yet been studied. We investigated this combination (single-dose or 4-week dosing) in diabetic ob/ob mice. Vehicle-corrected basal glucose showed greater reduction 1 h following exenatide + dapagliflozin than with exenatide or dapagliflozin alone, and stayed significantly lower for all groups versus vehicle over 3 h. During an oral glucose tolerance test, glucose excursion (30 min post-dose) was significantly lower for exenatide + dapagliflozin versus exenatide or dapagliflozin, or vehicle. Exenatide + dapagliflozin and exenatide, but not dapagliflozin alone, reduced glucose excretion over 24 h versus vehicle. After dosing for 4 weeks, exenatide, dapagliflozin and exenatide + dapagliflozin similarly decreased haemoglobin A1c (HbA1c). Body weight was reduced only with exenatide or exenatide + dapagliflozin. The glomerular filtration rate was similar with exenatide, dapagliflozin and vehicle, and increased with exenatide + dapagliflozin. Optimized combinatorial dosing of these antidiabetic agents may provide additive glucose lowering in type 2 diabetes mellitus.

The Relationship between Hypomagnesemia, Metformin Therapy and Cardiovascular Disease Complicating Type 2 Diabetes: The Fremantle Diabetes Study

BackgroundLow serum magnesium concentrations have been associated with cardiovascular disease risk and outcomes in some general population studies but there are no equivalent studies in diabetes. Metformin may have cardiovascular benefits beyond blood glucose lowering in type 2 diabetes but its association with hypomagnesemia appears paradoxical. The aim of this study was to examine relationships between metformin therapy, magnesium homoeostasis and cardiovascular disease in well-characterized type 2 patients from the community.Methods and FindingsWe studied 940 non-insulin-treated patients (mean±SD age 63.4±11.6 years, 49.0% males) from the longitudinal observational Fremantle Diabetes Study Phase I (FDS1) who were followed for 12.3±5.3 years. Baseline serum magnesium was measured using stored sera. Multivariate methods were used to determine associates of prevalent and incident coronary heart disease (CHD) and cerebrovascular disease (CVD) as ascertained from self-report and linked morbidity/mortality databases. 19% of patients were hypomagnesemic (serum magnesium <0.70 mmol/L). Patients on metformin, alone or combined with a sulfonylurea, had lower serum magnesium concentrations than those on diet alone (P<0.05). There were no independent associations between serum magnesium or metformin therapy and either CHD or CVD at baseline. Incident CVD, but not CHD, was independently and inversely associated with serum magnesium (hazard ratio (95% CI) 0.28 (0.11–0.74); P = 0.010), but metformin therapy was not a significant variable in these models.ConclusionsSince hypomagnesemia appears to be an independent risk factor for CVD complicating type 2 diabetes, the value of replacement therapy should be investigated further, especially in patients at high CVD risk.

Targets for Glycemic Control

Targets for Glycemic Control

Daily n-3 fatty acid supplements did not reduce CV events in high-risk patients with dysglycemia

ACP Journal Club18 September 2012Daily n-3 fatty acid supplements did not reduce CV events in high-risk patients with dysglycemiaEllis Lader, MDEllis Lader, MDMid Valley Cardiology, New York University School of Medicine, Kingston, New York, USA (E.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-6-201209180-02011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationORIGIN Trial Investigators, Bosch J, Gerstein HC, et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367:309-18. https://pubmed.ncbi.nlm.nih.gov/22686415Clinical Impact RatingsGIM/FP/GP: Cardiology: Endocrinology: References1 Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-86. [PMID: 8366922] Google Scholar2 Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-59. [PMID: 18539917] Google Scholar3 ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560-72. [PMID: 18539916] Google Scholar4 Duckworth W, Abraira C, Moritz T, et al; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129-39. [PMID: 19092145] Google Scholar5 Sobel BE, Hardison RM, Genuth S, et al; BARI 2D Investigators. Profibrinolytic, antithrombotic, and antiinflammatory effects of an insulin-sensitizing strategy in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Circulation. 2011;124:695-703. [PMID: 21768545] Google Scholar6 Knowler WC, Barrett-Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403. [PMID: 11832527] Google Scholar7 Daviglus ML, Stamler J, Orencia AJ, et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997;336:1046-53. [PMID: 9091800] Google Scholar Author, Article, and Disclosure InformationAffiliations: Mid Valley Cardiology, New York University School of Medicine, Kingston, New York, USA (E.L.)This article was published at Annals.org on 4 September 2012. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoGlargine did not reduce CV events more than standard care in patients with dysglycemia Ellis Lader Metrics 18 September 2012Volume 157, Issue 6Page: JC3-11KeywordsArrhythmiaFatty acidsGlucoseHbA1cHypoglycemiaInsulinMyocardial infarctionOilsType 2 diabetes ePublished: 18 September 2012 Issue Published: 18 September 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...