PocketPill app gives information on 1300 generic drugs and 70k brands available in Indian market. Classified drugs into Generic, Brand and Therapy Group.
PocketPill app gives information on 1300 generic drugs and 70k brands available in Indian market. Classified drugs into Generic, Brand and Therapy Group.
Salient Features, Indications, Dosage, Side Effects, Precautions, Warnings, Combinations and Price information of all the drugs in your pocket.
Find and Compare Brands available in the Indian market with it’s manufacturer details.
Superior User Interface, Works Faster, Works Offline and it’s FREE.
Featuring monthly articles from KOLs on Drug, Disease and Wellness
DPP-4 inhibition is a novel therapy of type 2 diabetes which improves islet cell function due to the increased concentrations of active GLP-1. This molecule stimulates insulin secretion and inhibits glucagon secretion. Since these effects target main pathophysiologic defects in type 2 diabetes, DPP-4 inhibition is an important treatment target for the disease. The therapy promises to be a solution to several of the currently unmet needs for treatment of the disease.
Clinical trials show the efficacy of the strategy, and more importantly has a favorable safety profile. There is low risk for adverse events or hypoglycemia. DPP-4 inhibition is therefore a novel and promising paradigm for treatment of type 2 diabetes.
Sitagliptin is a dipeptidyl-peptidase inhibitor (DPP-4 inhibitor) that has recently been approved for the therapy of type 2 diabetes. Like other DPP-4 inhibitors its action is mediated by increasing levels of the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP). It stimulates insulin secretion and inhibits glucagon secretion only when hyperglycemia is present.
The reduction in HbA1c is ≈0.6% to 1.0% from baseline levels of 7.5% to 8.7% over 6 to 12 months therapy. Sitagliptin like other DPP -4 inhibitors has a favorable safety profile and is highly tolerable.
Sitagliptin may be used in the early stages of type 2 diabetes in combination with metformin or other treatments in subjects with inadequate glycemic control on these treatments alone. Sitagliptin may also be used in monotherapy and, finally, sitagliptin may be used in combination with insulin in more advanced stages of the disease.
The occurrence of hypoglycemia is rare, which makes it of special interest in early stages of diabetes as well as in elderly patients.
Sitagliptin is the first orally-bioavailable selective dipeptidyl peptidase 4 (DPP4 ) inhibitor that was discovered through the optimization of a class of -amino-acid-derived DPP4 inhibitors. It competitively lowers DPP4 activity in a sustained manner following once daily administration, preserves the circulating levels of intact GIP and GLP1 following meals in both acute and chronic studies and reduces blood glucose levels without significant increases in hypoglycaemia.
Figure 1 | Sitagliptin Phosphate (Place the given image)
The safety and efficacy of sitagliptin as a monotherapy and in combination with existing antidiabetic agents was assessed in four randomized double-blind placebo-controlled clinical trials that involved more than 2,000 patients with T2DM. Several measurements relevant to glycaemic control were evaluated, including the mean change from baseline in glycated haemoglobin (HbA1C) levels — an indicator of average blood-sugar levels for the past 3 months.
Sitagliptin as a monotherapy at dose of 100 mg daily significantly reduced HbA1C, with few adverse events, and no significant increase in hypoglycaemia. The extent of HbA1C reduction was proportional to the starting HbA1C, and no significant weight gain was observed in 24-week monotherapy studies. Sitagliptin reduced both fasting and postprandial glycaemia, in association with improvements in the proinsulin/insulin ratio and homeostatic model assessment of -cell function (HOMA-B).
For patients who did not achieve adequate glycaemic control on at least 1,500 mg per day of metformin (mean HbA1C of 8%), the addition of sitagliptin 100 mg daily resulted in 47% of patients achieving a HbA1C of 7%, compared with 18.3% of placebo-treated subjects. Sitagliptin has also been shown to be effective when combined with metformin as initial therapy for T2DM.
Sitagliptin is approved as an adjunct to diet and exercise to improve glycaemic control in patients with T2DM, either as a monotherapy, or in combination with metformin or a peroxisome proliferator-activated receptor- agonist (for example, thiazolidinediones) when the single agent does not provide adequate glycaemic control. It can also be combined with insulin. Caution should be exercised in renal failure. Combination with sulfonylureas and insulin should be monitored as protective response to hypoglycemia caused by these agents is blunted by sitagliptin.
Sitagliptin may be taken with or without food as prescribed. The recommended dose of sitagliptin is 100 mg once daily.
The rise in obesity is driving a rapid upward trend in diabetes prevalence, particularly in developed countries. More than 200 million adults have T2DM (with an estimated 70 million in the United States and Europe), and there is a high degree of under-diagnosis and sub-optimal treatment. This epidemic is believed to result from both genetic and lifestyle factors causing a state of high insulin resistance. Available treatments focus on reducing hyperglycemia and improving insulin sensitivity. These modalities are attractive in theory, as they appear to target the primary defects associated with type 2 diabetes. However, despite the wide array of treatment options available, glycemic control declines over time. Unattainable glycemic control is often a result of ongoing deterioration of beta-cell function.
Sitagliptin probably tries to fill this unmet need by improving blood sugar control without affecting beta cell function when started early
Metformin is widely viewed as the initial drug of choice for the treatment of T2DM, owing to its long 30-year track record, efficacy, safety and low cost. However, many physicians now advocate initiating therapy of T2DM with at least two drugs to obviate the monotherapy failure that accompanies prolonged metformin use in the majority of treated patients.
There are at least seven different classes of agents that can be used in combination with metformin, including sulphonylureas, glitinides, -glucosidase inhibitors, thiazolidinediones, insulin (injected or inhaled), the GLP1R agonist exenatide and the DPP4 inhibitor sitagliptin.
Clinician has to choose amongst these agents based on the balance between ease of use, efficacy, safety, long-term durability and cost of therapy. Unfortunately, there is little information available from randomized-control trials directly comparing different agents when added to metformin.
Insulin secretagogues, such as the sulphonylureas and glitinides, are inexpensive but are associated with weight gain and hypoglycaemia, which can be particularly problematic in elderly patients.
The -glucosidase inhibitors are effective and safe, but are frequently associated with gastrointestinal side effects that limit their tolerability.
Thiazolidinediones improve insulin action with a low risk of hypoglycaemia and have appealing long-term durability, but the side effects of fluid retention, weight gain and cardiovascular side effects might be problematic for many patients.
Exenatide produces comparable glycaemic control with weight loss versus weight gain seen with insulin in head-to-head studies. However, the need for twice-daily injections and mild-to-moderate nausea might be challenging for some patients.
Sitagliptin and other DPP -4 inhibitors have shown emerging data with its ease of use, favourable adverse-event profile and lack of hypoglycemia or weight gain are additional attractive features. However cost is a little high. Further studies are needed to define the long-term efficacy and safety of sitagliptin, and to determine its relative merit compared with the growing number of options now available for the treatment of T2DM.
Sitagliptin and vildagliptin have been demonstrated to significantly reduce HbA1c when used as monotherapy. However, these reductions are typically not as significant as those achieved with more traditional therapies.
Furthermore, monotherapy studies published to date have included patients with relatively mild elevations in HbA1c levels at baseline. Thus, there are few data on the efficacy of these agents as monotherapy in patients with poorly controlled disease. Advantages of these agents include the ability to achieve sustainable reductions in HbA1c, few adverse events, neutral effect on body weight, and a once-daily oral dosing regimen. In addition, this class may preserve or even reverse the decline in beta-cell function that is observed in patients with diabetes. Further long- term data are required to support the use of these agents early in treatment. Potential disadvantages include cost and the relative lack of long-term safety and efficacy data.
In clinical studies, DPP-IV inhibitors have generally been well tolerated. Reported events are often mild and include nasopharyngitis, upper respiratory tract infection, headache, and cough.
Clinical trials have indicated that DPP-IV inhibitors generally do not cause severe hypoglycemia or weight gain. This is likely secondary to the mechanism of action of these agents; insulin secretion is stimulated in a dose- dependent manner, thereby minimizing hypoglycemia and resulting weight gain. The weight neutrality of this class distinguishes these agents from other commonly used antidiabetic medications, including insulin, sulfonylureas, and thiazolidones.
DPP-IV has the potential to cleave other substrates besides GLP-1.34 These substrates include hormones, neuropeptides, and chemokines. In many cases, this cleavage product are inactive. DPP-IV inhibitors prolong the action of neuropeptides such as substance P and macrophage-derived chemokines. Prolonging these messengers may produce inflammation (effect on substance P), increase blood pressure (effect on neuropeptide Y), or cause allergic reactions (effect on chemokines). These theoretical concerns have not yet been observed in animal or human studies.
Hypoglycemia is rare (3%) during treatment with DPP-4 inhibitors as monotherapy or in combination with metformin or thiazolidinediones. The low degree of hypoglycemia is especially seen when compared with the risk of hypoglycemia during treatment with sulfonylurea . This is explained by the glucose-dependency of the islet effects of GLP-1; hence when glucose levels are reduced the effects of GLP-1 in stimulating insulin secretion and inhibiting glucagon secretion vanish.
In contrast, hypoglycemia was shown to be more common when sitagliptin was added to ongoing glimepiride; the incidence of hypoglycemia was 12% versus 2% in the group given glimepiride alone. The potential risk for hypoglycemia when combining sitagliptin and sulfonylureas may be due to an uncoupling mechanism of sulfonylureas of the glucose dependency of the islet actions by GLP-1. This risk needs, however, to be evaluated in more detail.
If increased frequency of hypoglycemia when combining sitagliptin with a sulfonylurea is confirmed, a clinical consequence is that the dose of sitagliptin or sulfonylureas should be reduced when these are used in combination. Similarly, when combined with insulin, there was an increased risk for hypoglycemia by sitagliptin.
The diagnostic category of impaired fasting glucose (IFG) and impaired glucose tolerance ( IGT ) was established in an effort to identify populations at risk for developing future type 2 diabetes mellitus (T2DM) and are regarded as pre-diabetic stage.
Both IGT and IFG are associated with increased risk of developing T2DM, but the thresholds of risk vary among different populations and an even lower diagnostic threshold of IFG may be appropriate than an earlier cutoff of 110 mg/dl.
IFG has been linked with an increased risk of cardiovascular events. Both IGT and IFG are associated with resistance to insulin and increased insulin secretion; they do not represent identical patient populations and are not equivalent in predicting development of T2DM or cardiovascular events. IFG and IGT have been associated with other constellation of insulin resistance, including dyslipidemia, hypertension, abdominal obesity, micro-albuminuria, endothelial dysfunction, and markers of inflammation and hyper-coagulability, comprising the metabolic syndrome. These components have been associated with progression to T2DM, cardiovascular disease and increased mortality.
The foundation of treatment for IGT, IFG, and the metabolic syndrome is lifestyle modification, including both dietary change and routine exercise. Several clinical trials have proven that lifestyle modification is the most efficacious strategy to prevent progression to T2DM.
Alternative treatments include pharmacotherapy with metformin or acarbose, both of which have been demonstrated to decrease the development of T2DM.
Ongoing clinical trials are evaluating therapies, including angiotensin converting enzyme inhibitors, angiotensin receptor antagonists to prevent both T2DM and cardiovascular events.
In combination with lifestyle modification, these therapies offer hope for effective prevention of T2DM and its consequences in high-risk patients.
Impaired fasting glucose typically characterized by hyperglycemia and insulin resistance, is considered to be a precursor and a stage in the future development of type 2 diabetes mellitus and an important risk factor for cardiovascular disease.
Prevention of disease is important to avert an epidemic type 2 diabetes mellitus (T2DM) and identifying target population at highest risk helps in channeling the resources. Improved understanding of the molecular processes in the development of insulin resistance has opened new frontiers for identification and characterization of patients at risk for T2DM, associations with other disease processes, and development of novel therapies. Populations at high risk can be identified using simple markers of abnormal glucose metabolism like fasting sugar.
Lifestyle modification and some pharmacological therapies have a favorable effect on reducing the risk for development of T2DM in these patients. Large-scale clinical trials are ongoing to evaluate the effect of pharmacological agents on prevention of the onset of T2DM and its complications.
Community preventive measures include healthy lifestyle and exercise measures, healthy diet low in fat and sugars and high in fibers, fruits and vegetables.
Impaired fasting glucose was previously defined as a fasting plasma glucose of 110 to 125 mg/dl (6.1 to 6.9 mmol/L ) but recently ADA and other bodies have redefined it as 100 to 125 mg/dl (5.6 to 6.9 mmol/L)
The World Health Organization (WHO) has recommended that people with an HbA1c of 6.0-6.5% (42−47 mmol/mol) are also at high risk of diabetes.
Patients with impaired fasting glucose at High Risk for Type 2 diabetes
Several drug trials using commonly available safe anti-diabetic agents have been done to prevent progression to overt diabetes. These include metformin, pioglizatone, orlistat and ACE - inhibitors/ ARBs. The risk reduction of diabetes incidence has ranged from 14% to 72%.
Walking is one of the easiest ways to boost physical activity and improve one’s health. It is a form of aerobic exercise. Any Aerobic exercise improves or is intended to improve the efficiency of the body's cardiovascular system in absorbing and transporting oxygen.
Regular walking has been shown to reduce your risk of heart disease and stroke. It lowers levels of LDL (bad) cholesterol while increasing levels of HDL (good) cholesterol and keeps blood pressure in check.
Anything that raises our heart rate is an aerobic workout improving our cardiovascular health. Walking briskly for up to 30 minutes can help prevent and control the high blood pressure that causes stroke – this risk is reduced to the extent of 27 % .
A regular walking habit can bring down the risk of developing type 2 diabetes, asthma and certain type of cancers. A study showed that taking more steps every day could help ward off diabetes. Regular exercise such as walking could reduce risk by up to 60 per cent. Those of us who are active have around 20 % lower risk of developing cancer of the colon, breast and uterus than less active individuals.
"If you’re trying to lose weight, you need to burn about 600 calories a day more than you’re eating". "Putting one foot in front of the other is one of the easiest ways to do that." A person weighing 60kg burns 75 calories simply by strolling at 2mph for 30 minutes. The study by Gordon-Larsen et al, the first study to examine the independent effects of walking on long-term weight control. This is of great interest to public health, because walking is inexpensive, accessible, and well accepted among adults. This prospective cohort study monitored young adult men and women for 15 y into middle adulthood. Other types and amounts of physical activity and dietary intake were controlled for in the analysis.
Results indicate that walking attenuates weight gain over the 15-y period. The greatest benefit was seen for women with the heaviest baseline weight. For these women, those with the highest walking levels resulted in weight gain < 8 kg over 15 y. Furthermore, there appears to be a dose effect, with 2 h of walking per week being better than none, and 4 h of walking better than 2h. In addition, it was also found that for all subjects, higher walking levels were associated with a higher likelihood of weight loss and weight maintenance. This demonstrates that walking has an independent protective effect on weight gain.
Dementia affects one in 14 people over 65 and one in six over 80 and is a growing health problem. Being active has a protective effect on brain function and regular exercise reduces dementia risk by up to 40 per cent.
"Walking is a weight-bearing activity”. "It stimulates and strengthens bones, increasing their density – really important, especially for women. It also helps maintain healthy joints so may protect from conditions such as arthritis."
Walking outside in daylight will be boosting ones body’s stores of vitamin D – a nutrient that’s hard to get from food, but that we can synthesize from exposure to sunlight. Many people are deficient in vitamin D and it’s a nutrient that plays a big role in everything from bone health to immunity. While sun safety is still important experts agree that exposing as much skin as you can to the sun, little and often and without burning, will help to produce sufficient vitamin D.
It might seem like a paradox but a brisk walk is one of the best natural energizers around. It boosts circulation and increases oxygen supply to each and every cell in your body, helping you to feel more alert and alive. It wakes up stiff joints and eases muscle tension so you feel less sluggish.
The ability of exercise to boost mood is undisputed. Studies have shown regular, moderate-intensity exercise (such as brisk walking) to be as effective as antidepressants in cases of mild to moderate depression. Getting active releases feel-good endorphins into the bloodstream, reducing stress and anxiety.
Walking has a huge impact on reduction of all cause mortality. Various studies have shown an association between walking and reduction in deaths from all causes, ranging from 9-30 percent depending on frequency and length of walking activities.
Medical experts say inactivity poses as great a health risk contributing to heart disease, diabetes, hypertension, cancer, depression, arthritis and osteoporosis. Regular exercise has been shown to combat the ongoing damage done to cells, tissues and organs that underlie many chronic conditions. Indeed, studies have found that exercise can lower blood pressure, reduce bad cholesterol, and cut the incidence of Type 2 diabetes. Many studies have shown the universal fact that moderate physical activity -- such as walking -- is associated with positive health results.
How much physical activity to recommend?
METs are a commonly used term to assess the level of physical activity. They are metabolic equivalents and measure physical activity in multiples of resting energy expenditure. For example, an activity that is 2 MET has an energy expenditure of two times resting energy required.
A good starting target for your patients is to increase walking by at least 2km/day for 30 min or 2400 steps/day.
The key is to walk fairly briskly -- 3 to 4 miles per hour -- and for 30-60 minutes at least five days a week. This can cut your risk of heart disease by 40 percent.
In order to lose weight, at least 60-90 minutes of daily, moderate-intensity walking is necessary, according to guidelines from the American College of Cardiology and the American Heart Association.
It is advisable to get one checked/evaluated with basic cardio respiratory function assessment before starting walking or exercise from sedentary life style, especially in middle aged individual.
Using step counters to measure your patients walking
Electronic step counters (pedometers) are being increasingly used for promoting walking. These inexpensive devices are worn on the waist and simply count the number of steps taken each day. Step counters allow the patients to continuously monitor their progress in achieving their physical activity goal during the day.
Also most modern smart phones have motion sensors, which count the number of steps per day using many free apps available in both iOS and Google play store.
Alternative Suggestions for Walking if any Orthopedic or Neurological Problem:
Alternative Suggestions for People Working in Offices (busy people!!!):
Cardiac rehabilitation and secondary prevention of coronary artery events