Assessment of the efficacy and tolerability of a fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg in diabetic dyslipidaemia in adult Indian patients

Type 2 diabetes mellitus is associated with a marked increase in the risk of coronary heart disease (CHD) or stroke (by a factor of two to three compared with non-diabetic patients), and cardiovascular disease (CVD) accounts for the majority of deaths among patients with diabetes. A new fixed dose combination containing atorvastatin 10 mg + metformin SR 500 mg is being introduced in the Indian market for the treatment of dyslipidaemia in diabetic patients. The present study was therefore undertaken to assess efficacy, safety and tolerability of a fixed dose combination of atorvastatin 10mg + metformin SR 500mg in adult Indian patients with diabetic dyslipidaemia. The final protocol was approved by relevant ethics committee before the initiation of study. Informed consent was obtained from all the patients prior to enrollment in study. The total duration of study was 14 weeks including two weeks dietary run in period. Patients fulfilling the selection criteria received a single oral tablet of fixed dose combination of atorvastatin 10mg + metformin SR 500mg once daily for 12 weeks. The primary efficacy parameters were assessed by evaluating reduction in fasting and postprandial plasma glucose concentration levels at baseline and thereafter at each follow up visit at 2, 4, 8 and 12 weeks and plasma lipid profile and glycosylated Hb levels at baseline and end of study. The secondary efficacy parameters were assessed by evaluating percentage change from baseline at the end of the study (week 12) in the plasma concentration of the various lipid parameters such as total, HDL-, LDL- and very low density (VLDL)-cholesterol, triglycerides, Apo B, Apo A1, TC/LDL ratio, LDL/ HDL ratio, and percentage of patients achieving LDL-cholesterol goals as per NCEP ATP III guidelines. A total of 213 patients were enrolled in the study. Of these seven patients were lost to follow-up and considered as drop-outs. Therapy with the fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg resulted in a significant reduction in the mean plasma fasting and postprandial glucose levels (35 and 38.8% respectively). There was a steep fall in the HbA1c levels from baseline levels of 8.76% to 6.74% (23.1%). There was also a significant (p < 0.05) reduction in mean total cholesterol (31.2%), LDL cholesterol (35.4%), VLDL-cholesterol (19.6%) and a significant increase HDL-cholesterol (9.5%). Thus there appeared to be trend towards reducing atherosclerosis following therapy with the fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg. Mean body mass index was significantly reduced in the patients in the present study following therapy with the study drugs. The fixed dose combination of atorvastatin with metformin was well tolerated with mostly gastro-intestinal adverse events being reported in the current study. Moreover, most of the adverse events were mild to moderate in intensity and disappeared with continued treatment. In conclusion, the results of the present study suggest that, the fixed dose combination of atorvastatin 10 mg + metformin SR 500 mg is efficacious and well tolerated therapeutic modality in patients with diabetic dyslipidaemia. Furthermore this combination offers dosage convenience to the patient and by virtue of its dual mode of action is a useful addition to the therapeutic armamentarium for patients with diabetic dyslipidaemia.     

An open prospective study on postmarketing evaluation of the efficacy and tolerability of diacerein in osteo-arthritis of the knee (DOK)

According to World Health Organisation osteo-arthritis is the second commonest musculoskeletal problem in the world. Diacerein has been recently introduced in India for the treatment of osteo-arthritis. In view of the ulcerogenic potential of NSAIDs and the cardiotoxicity problems associated with COX-2 inhibitors, diacerein has the potential of being a non-ulcerogenic and non-cardiotoxic alternative respectively to NSAIDs and of COX-2 inhibitors in the treatment of osteo-arthritis. The present study was, therefore, undertaken to evaluate the efficacy and tolerability of diacerein in the treatment of osteo-arthritis. A total 7923 patients with osteo-arthritis of the knee fulfilling the selection criteria were enrolled in this open-label, multicentric postmarketing surveillance study. After a wash-out period of one week, patients were treated with 50mg diacerein tablets administered twice daily for 12 weeks. The primary efficacy variable of the present study was to assess the improvement in the visual analogue scale (VAS) scores for pain. The secondary variable was improvement in patients' and physicians' global assessment of efficacy of therapy. Results indicated that over the 12-week study period, diacerein 50mg tablets provided significant and sustained reduction the VAS pain scores. At baseline, VAS scores were 6.70 +/- 1.78. By the end of the 4th week, there was a significant reduction in the mean VAS scores by 21.8% and by the end of the study the mean VAS scores were further significantly reduced by 59.9%. As per the patients global assessment of treatment, 82.3% of the patients reported good to very good improvement at the end of 12 weeks therapy with diacerein. Similar responses were also recorded by the treating patients. Thus by the end of 12 weeks therapy, according to the physicians 85.5% of the total cases treated with diacerein were rated as having good to very good improvement. Therapy with diacerein was well tolerated and only 5.44% of the patients had an adverse event after treatment with diacerein. The most common adverse events were diarrhoea (2.3%), gastritis (0.99%), nausea (0.61%), abdominal pain or discomfort (0.44%) and vomiting (0.3%). The severity of the adverse events was mild in all the cases and disappeared with continued treatment. None of the patients dropped out of the study on account of adverse events or lack of efficacy. Thus, in conclusion, the results of the present study in a large population of Indian patients indicates that diacerein constitutes a novel approach to the treatment for the short- and long-term symptomatic management in Indian patients with osteo-arthritis of the knee.     

Piper betel Linn (betel vine), the maligned Southeast Asian medicinal plant possesses cancer preventive effects: time to reconsider the wronged opinion

Since antiquity, Piper betel Linn (betel vine; family Piperaceae) has been an important medicinal agent in the various traditional and folk systems of medicine in Southeast Asia countries. The leaves are the most valued plant part and in the past were routinely used as a chewing agent to prevent halitosis. The leaves are also supposed to harden the gum, conserve the teeth and to prevent indigestion, bronchitis, constipation, congestion, coughs and asthma. Innumerable scientific studies have validated the ethnomedicinal claims. Betel leaves are an integral component of the betel quid that consists of areca nut (Areca catechu Linn.), tobacco (Nicotiana tabacum L) and slaked lime; a highly abused agent with carcinogenic properties. Regular chewing of betel quid is associated mainly with oral cancer and detail studies with individual constituents of the quid have shown that both tobacco and areca nut are carcinogenic, while slaked lime is shown to promote the process of carcinogenesis. However unlike other constituents of the betel quid, the betel leaves devoid carcinogenic effects and on the contrary possesses cancer preventive effects including against the carcinogens present in tobacco. This review for the first time provides information on cancer preventive effects and also addresses the various mechanisms which might be involved.