The discovery of metformin as an anti-diabetic drug spans three centuries-beginning in the herb, Galega officinalis in the 17 ^th century and ending in its launch as "Glucophage" in the 20 ^th century. Extract from the leaves of G. officinalis was used to treat many ailments such as fever, plague and symptoms of diabetes. The herbal extract contains guanidine and galegine as major chemical components. These compounds, although had an anti-diabetic effect, were too toxic for clinical use. Discovery of antimalarial drug, paludrine which also had blood glucose lowering activity, at the Imperial Chemical Industries, UK prompted evaluation of paludrine analogues, as potential anti-diabetic agents. This speculation was also based on the structure of paludrine, which partly resembled galegine, a compound present in the extract of G. officinalis. This development coupled with Garcia's positive results using flumamine, a guanidine analogue, on 'flu' fever accelerated the evaluation of guanidine and galegine analogues for anti-diabetic activity. These efforts culminated in the discovery of metformin, introduced as 'Glucophage', by Jean Sterne, in 1957. In this article, we have highlighted the journey of metformin from a common countryside herb to its present day status of a 'Wonder Drug' sitting at the bedside of diabetic patients.

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Objective: The aim was to study herb-drug interaction of two ayurvedic formulations - DMFN01 (Nisha-Amalaki) powder and DMFN02 (Mamejava) ghanavati with metformin at a single dose in healthy volunteers. Materials and Methods: This was an open-labelled, single dose, crossover, and randomized volunteer study. Healthy volunteers were studied in two groups (6/group). Volunteers were randomized to oral metformin (500 mg single dose) alone or with concurrent DMFN01 (10 g), or DMFN02 (750 mg). Venous blood samples were collected at different time points from 0 to 24 h. Plasma metformin concentrations were measured by high performance liquid chromatography coupled with an ultraviolet detector. Results: Simultaneous administration of DMFN01 with metformin showed a reduction in the mean area under the curve (AUC [0-24 h]) of metformin by 51% (P < 0.002) when compared with metformin alone. However, co-administration of DMFN02 did not show any significant difference in the mean AUC of metformin (P = 0.645). One volunteer had a reduction of 41% in AUC of metformin with DMFN 02. Conclusions: These data raise relevant questions on therapeutic control of hyperglycemia when DMFN01 choorna is given concurrently with metformin. Based on known absorption pattern of metformin an interval of 2 h between the oral doses of metformin and ayurvedic formulations would be advisable to avoid interactions. In reverse pharmacological studies, at an early stage, such interaction studies are desirable.

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Aim: We aimed to diagnose latent diabetic hypothyroid patients presenting with symptoms of metabolic syndrome (MS) based on the Adult Treatment Panel-III (ATP-III) guidelines. Background: Type 2 diabetes mellitus (DM) coexisting with thyroid disorders is difficult to manage. With an ever-increasing incidence of both these disorders and an increasing risk of secondary complications due to their coexistence, newer correlative studies are needed for the early diagnosis of these diseases. Subjects and Methods: The present study was conducted on 100 healthy controls and 150 newly diagnosed hypothyroid patients. The patients were selected based on symptomatology and thyroid function tests. They were then analyzed for body mass index (BMI), blood pressure, fasting blood sugar (FBS), fasting serum insulin, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and apolipoprotein B (apo-B) and apolipoprotein (apo-A ₁ ). Statistical Analysis: Analysis was done using the Students "t" test and Spearman's coefficient of correlation. Results: For hypothyroid patients who presented with raised BMI, diastolic hypertension and dyslipidemia were further investigated for underlying latent diabetes. Of the total hypothyroid patients, 53.3% had raised FBS, 48% had diastolic hypertension, 86.6% had hypertriglyceridemia and 66.67% patients fulfilled three conditions for MS as per the ATP-III guidelines. There was highly significant correlation of serum insulin and HOMA-IR with lipid fractions and cardiovascular disease (CVD) risk ratios (total cholesterol/high-density lipoprotein cholesterol) and apo-B/apo-A ₁ in hypothyroid patients. Conclusion: All hypothyroid patients should be closely watched for presence of DM and MS for prevention of atherogenic dyslipidemia, which may lead to CVDs. The estimation of serum insulin, apo-A ₁ and apo-B, along with the traditional lipid profile may be useful in such patients.

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Introduction: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder, which can cause various reproductive complications and is associated with metabolic syndrome. In India, strong comparative evidence of oral contraceptive pills (OCP), metformin or their combination in treatment of polycystic ovarian disease is lacking. Objectives: The objective of this study is to compare the efficacy and safety of metformin alone, OCP containing drospirenone or a combination of OCP and metformin in patients with PCOS. Materials and Methods: This was an open-label, randomized, parallel group, and comparative three-arm prospective study, in 60 patients. Patients either received OCPs containing etinyl estradiol plus drospirenone, metformin or combination of OCPs plus metformin for 6 months. Luteinizing hormone: Follicle stimulating hormone (LH:FSH) ratio, serum insulin level, ovarian morphology, body mass index (BMI), acceptance of treatment, regularization of the menstrual cycle and improvement in acne and hirsuitism were evaluated. Results: In patients receiving metformin either as monotherapy or in combination showed significant improvement in BMI. All the study medicines were effective in significantly decreasing ovarian volume, LH/FSH ratio and serum insulin level. Improvement in acne was better in patients receiving OCPs either as monotherapy or in combination with metformin. Improvement in hirsuitism and regularization of the menstrual cycle was highest in patients receiving combination treatment. Acceptance of treatment was maximum in patients receiving monotherapy of OCPs. The total incidence of adverse events was 16.7% (15%, 15% and 20% in OCP, metformin, and combination group, respectively). Conclusion: OCPs containing ethinylestradiol plus drospirenone, metformin, and combination of both are effective and well tolerated in the management of PCOS. Metformin either as monotherapy or combination can be preferred in cases with high BMI. Combination of metformin plus OCP regularizes menstrual cycle better than monotherapy of either drug.

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Obesity is a fast growing pandemic, for which there are limited pharmacological options. This review describes the functional impairment of glucagon-like peptide (GLP-1) observed in obesity, and assesses the impact of the novel class of glucagon-like peptide-1 receptor agonists (GLP-1- RA) on weight. It discusses weight loss observed with GLP-1- RA use in subjects with and without diabetes, and assesses their safety and tolerability

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Obesity and osteoarthritis are globally reaching epidemic proportions. Their concomitant association is well-known. The cumulative impact of these conditions on morbidity and the quality-of-life is sizeable, particularly for the aged. Obesity leading to osteoarthritis of the weight-bearing joints is well-appreciated. Inversely, however it is less emphasised that osteoarthritis of big joints of the lower limbs contributes to obesity because of the resultant physical inactivity. The increased adiposity is known to secrete proinflammatory cytokines that adds to the biomechanical cause of osteoarthritis. Besides mechanical and inflammatory mechanisms, genetic factors also play a causative role in both obesity and osteoarthritis as separate and concomitant disorders. The genetic and epigenetic mechanisms are gradually being unravelled for the comorbidity of obesity and osteoarthritis. Thus, the molecular pathophysiology of the concomitant existence of obesity and osteoarthritis is highly intriguing. Identifying the appropriate choice and sequence of therapeutic targets for reversal of this complex pathogenesis is a challenging task. Ayurvedic understanding of this comorbidity and experiential therapeutic base can offer a strategy for the prevention and management of the disorders. "Sthaulya" and "Sandhigatavata" are the respective clinical syndromes, described in Ayurveda for obesity and osteoarthritis. The imbalance in the respective "Dhatvagni" (metabolic paths) of "Meda-Dhatu" (adipose tissue) and "Asthi-Dhatu" (bone tissue) is the putative central pathogenetic mechanism involved for the comorbidity. The present article analyses some of the insights and experience from Ayurveda so as to provoke a meaningful debate on the opportunities for integrative care for obesity related osteoarthritis through reverse pharmacology path.

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