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Objective: To characterize the adoption of antiobesity pharmacotherapies, as compared with that of the newest antidiabetes pharmacotherapy, subtype 2 sodium-glucose transport protein inhibitors (SGLT2s), among prescribers in the United States., Methods: A retrospective analysis of 2012 to 2015 data extracted from the IMS Health National Prescription Audit™ and Xponent™ assessed adoption rates of antiobesity pharmacotherapies and SGLT2s., Results: The number of dispensed antidiabetes prescriptions was 15 times the number of dispensed antiobesity prescriptions. The antiobesity market share was: 74.0% phentermine, 18.6% new antiobesity pharmacotherapies. The mean increase in prescriptions/month were: 25,259 for SGLT2s, 5,154 for new antiobesity pharmacotherapies, and 2,718 for phentermine. Medical specialties prescribing the majority of the analysis medications were Family Medicine/General Practice and Internal Medicine. Endocrinology had the highest prevalence of prescribers of any subspecialty., Conclusions: The adoption rate of SGLT2s was nearly exponential, while the adoption rate of new antiobesity pharmacotherapies was linear. Considering the relative prevalence of obesity to diabetes and that obesity is a major cause of diabetes, these results are paradoxical and suggest systematic barriers against the prescribing of antiobesity pharmacotherapies. The under-prescribing of antiobesity pharmacotherapies is widely acknowledged, but this is the first prescription data of these new medications to demonstrate its extent in the United States., (© 2016 The Obesity Society.)

Objective: Autophagy is a critical cellular system for removal of aggregated proteins and damaged organelles. Although dysregulated autophagy is implicated in the development of heart failure, the role of autophagy in the development of diabetic cardiomyopathy has not been studied. We investigated whether chronic activation of the AMP-activated protein kinase (AMPK) by metformin restores cardiac function and cardiomyocyte autophagy in OVE26 diabetic mice., Research Design and Methods: OVE26 mice and cardiac-specific AMPK dominant negative transgenic (DN)-AMPK diabetic mice were treated with metformin or vehicle for 4 months, and cardiac autophagy, cardiac functions, and cardiomyocyte apoptosis were monitored., Results: Compared with control mice, diabetic OVE26 mice exhibited a significant reduction of AMPK activity in parallel with reduced cardiomyocyte autophagy and cardiac dysfunction in vivo and in isolated hearts. Furthermore, diabetic OVE26 mouse hearts exhibited aggregation of chaotically distributed mitochondria between poorly organized myofibrils and increased polyubiquitinated protein and apoptosis. Inhibition of AMPK by overexpression of a cardiac-specific DN-AMPK gene reduced cardiomyocyte autophagy, exacerbated cardiac dysfunctions, and increased mortality in diabetic mice. Finally, chronic metformin therapy significantly enhanced autophagic activity and preserved cardiac functions in diabetic OVE26 mice but not in DN-AMPK diabetic mice., Conclusions: Decreased AMPK activity and subsequent reduction in cardiac autophagy are important events in the development of diabetic cardiomyopathy. Chronic AMPK activation by metformin prevents cardiomyopathy by upregulating autophagy activity in diabetic OVE26 mice. Thus, stimulation of AMPK may represent a novel approach to treat diabetic cardiomyopathy.

The efficacy of Momordica charantia (MC), Eugenia jambolana (EJ), Tinospora cordifolia (TC) and Mucuna pruriens (MP) was assessed in the prevention of murine alloxan dibetic cataract. Alloxan (120 mg/kg) was used as the diabetogenic agent. While controls and diabetic controls did not receive any plant extract, treated rats received lyophilized aqueous extract of MC and EJ (200 mg/kg p.o.), alcohol extract of TC (400 mg/kg) and MP (200 mg/kg p.o.) every day until 4 months. Serum glucose concentration was assessed and cataracts examined with both the naked eye and through a slit lamp. Of the eight animals in the diabetic control group, four developed cortical cataract (stage IV) by day 90 while the remaining four developed it by day 100. The incidence rate of cataract in MC, EJ, TC and MP treated groups at 120 days was only 0, 0, 1 and 2. Oral feeding of MC, EJ, TC and MP extracts for 1 month produced a fall of 64.33%, 55.62%, 38.01% and 40.17%, respectively, in the serum glucose levels in comparison with the 48 h level. After 2 months of treatment, the respective values were 66.96%, 59.85%, 40.41% and 45.63%. MC and EJ prevented the development of cataract while the protective effect was less with TC and MP along with a significant reduction of plasma glucose levels (p < 0.001)., (Copyright 2002 John Wiley & Sons, Ltd.)

The hypoglycemic effect of the aqueous (Aq) extract of the bark of Pterocarpus marsupium (PM) and alcoholic (Alc) extract of seeds of Trigonella foenum-graecum (FG) and leaves of Ocimum sanctum (OS) was investigated in both normal and alloxan-induced diabetic rats. The Aq extract of PM (1 g/kg PO) significantly (P<0.001) reduced the blood sugar levels from 72.32+/-5.62 to 61.35+/-1.2 mg% 2 h after oral administration of the extract and also significantly lowered the blood glucose in alloxan diabetic rats from 202.91+/-5.44 to 85.22+/-11.28 mg% 21 days after daily oral administration of the extract (P<0.001). Similarly, reduction was seen with Alc extract of FG (74.33+/-4.77 to 60.56+/-1.9 in normal rats and 201.25+/-7.69 to 121.25+/-6.25 in diabetic rats) (P<0.001) and OS (204.48+/-11.0 to 131.43+/-7.86 in normal rats and 73.54+/-3.7 to 61.44+/-2.3 in diabetic rats) (P<0.001). In addition, the extract also showed a favorable effect on glucose disposition in glucose fed hyperglycemic rats.

The purpose of the study was to investigate the effects of daily oral feeding Momordica charantia (MC) (200 mg/kg), Eugenia jambolana (EJ) (200 mg/kg), Mucuna pruriens (MP) (200 mg/kg) and Tinospora cordifolia (TC) extracts for 40 days on blood glucose concentrations and kidney functions in streptozotocin (STZ)-diabetic rats. Plasma glucose levels, body weight, urine volume and urinary albumin levels were monitored on every 10th day over a 40-day period while plasma creatinine levels were assessed at the beginning and end of experiment. Renal hypertrophy was assessed as the ratio between the kidney weight and total body weight. Plasma glucose concentrations in STZ-diabetic mice were reduced by the administration of extracts of MC, EJ, TC and MP by 24.4, 20.84, 7.45 and 9.07%, respectively (P<0.005 for MC, EJ, MP and P<0.05 for TC). Urine volume was significantly higher (P<0.005) in diabetic controls and MC, EJ, MP and TC treatment prevented polyuria (P<0.001, 0.0001, 0.01 and 0.001, respectively). After 10 days of STZ administration urinary albumin levels (UAE) were over 6 fold higher in diabetic controls as compared to normal controls. Treatment with MC, EJ, MP and TC significantly prevented the rise in UAE levels from day 0 to 40 in comparison to diabetic controls (P<0.0001, 0.0001, 0.05, 0.05, respectively). Renal hypertrophy was significantly higher in diabetic controls as compared to non-diabetic controls. MC and EJ partially but significantly (P<0.05) prevented renal hypertrophy as compared to diabetic controls. TC and MP failed to modify renal hypertrophy. Results indicate that these plant drugs should be studied further.

Insulin resistance has been implicated as a major contributor to the development of hyperglycemia in NIIDM patients. Herbal extracts of Momordica charantia (MC) and Eugenia jambolana (EJ) have been shown to reduce hyperglycemia in diabetic animal models and human patients. However, no work has been done so far to assess their effect on insulin resistance. This study was undertaken to study the effects of different doses (100,200 and 400 mg per day) of alcoholic and aqueous extracts of MC and EJ on the metabolic parameters (body weight and serum glucose, insulin and triglycerides levels) of fructose fed rats. Fructose feeding for 15 days increased serum glucose and insulin levels markedly and triglycerides levels marginally vs. control (75.46+/-2.41 vs. 55.59+/-2.89 mg/dl, 6.26+/-1.27 vs. 15.04+/-2.43 mg/dl and 50.93+/-3.30 vs.41.1+/-3.33 mg/dl, respectively). Treatment with 400 mg per day of aqueous extracts of MC and EJ for 15 days substantially prevented hyperglycemia and hyperinsulinemia induced by a diet high in fructose (63.52+/-2.9 and 66.46+/-2.2 vs. 75.46+/-2.4, respectively).

In India, the decoction of kernels of Eugenia jambolana (EJ) and extracts of Tinospora cordifolia (TC) are used as a household remedy for diabetes. These also form constituents of many herbal formulations for diabetes that are marketed in this country. The anti-hyperglycemic effect of aqueous and alcoholic extracts as well as lyophilized powder of these two plants was evaluated in diabetic animals using different doses of diabetogenic agents for varying duration (21-120 days) so as to assess their effect in mild (plasma sugar>180 mg/dl, duration 21 days), moderate (plasma sugar>280 mg/dl, duration 120 days) and severe (plasma sugar>400 mg/dl, duration 60 days) diabetes mellitus. In the pilot study (mild diabetes), maximum reduction of 73.51 and 70.37% in glucose levels was seen in animals receiving 200 mg/kg per day of lyophilized powder of EJ and 400 mg/kg per day of aqueous extract of TC after 3 and 15 weeks of treatment, respectively. There percent reduction in glucose decreased significantly in the moderate and severe diabetes; 55.62 and 17.72% for EJ and 48.81 and 0% for TC at the similar time intervals. The alteration in hepatic and skeletal muscle glycogen content and hepatic glucokinase, hexokinase, glucose-6-phosphate and phosphofructokinase levels in diabetic mice were partially restored by EJ but not by TC. The mechanism of action of EJ and TC is discussed.