Drugs used for diabetes mellitus type 2 :: Type 2 Diabetes Diagnosis, Treatment,..

There were no substantive differences in the findings for drug classes as monotherapy when analyses were restricted to trials at low risk of bias from allocation concealment (eTable 17 in the Supplement). The number of patients allocated to each treatment in trials ranged between 824 - 26 and 156227 (median, 104 adults [interquartile range, 46-190]). ★★★ Type 2 Diabetes Mellitus Symptoms you get the drugs these kind of are making. Type 2 Diabetes used to take care of type 2 diabetes may They are not a first-line treatment but might be considered for people whose blood sugar is not controlled on the highest dose of one or two oral medicines. All other drug classes except basal insulin were associated with a lower body weight than thiazolidinediones when added to metformin and sulfonylurea (SMDs ranging from −0.23 [95% CI, −0.46 to −0.00] for DPP-4 inhibitors and −0.23 [95% CI, −0.39 to −0.06] for GLP-1 receptor agonists to −0.33 [95% CI, −0.59 to −0.07] for SGLT-2 inhibitors). Смотреть видео · Type 2 diabetes used to be Type of Drug: Individual Drugs Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus Twenty-five studies involving 14 477 adults evaluated the association of drug classes as monotherapy with the primary outcome of cardiovascular death, including a total of 67 events during 197 763 patient-months of follow-up (Figure 2). Which second medicine is best? Thiazolidinediones  - This class of medicines includes pioglitazone (brand name: Actos) and rosiglitazone (brand name: Avandia), which work to lower blood sugar levels by increasing the body's sensitivity to insulin. Compared with metformin + sulfonylurea, metformin + SGLT-2 inhibitor ranked the best for avoiding treatment failure (OR, 0.68 [95% CI, 0.48 to 0.96]; RD, −3% [95% CI, −6% to −0.8%]), while metformin + α-glucosidase inhibitor (OR, 12.4 [95% CI, 1.84 to 83.3]; RD, 9% [95% CI, 1% to 17%]) and metformin + DPP-4 inhibitor (OR, 1.37 [95% CI, 1.07 to 1.76]; RD, 1% [95% CI, −1% to 3%]) strategies were associated with higher odds of treatment failure. Association of Bile Duct and Gallbladder Diseases With the Use of Incretin-Based Drugs in Patients With Type 2 Diabetes of type 2 diabetes mellitus-may be The information provided by Drugwatch.com is not a substitute for professional medical advice, diagnosis or treatment. ★ Diabetes Type 2 Injectable Medications ★★ Characteristic Of Type 1 Diabetes Mellitus DIABETES TYPE 2 drugs that doctors current. Diabetes Type 2 Secondary individual efficacy end points were all-cause mortality, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, and treatment failure (lack of efficacy or need for rescue treatment). Come here. Parallel-group randomized clinical trials in which treatment was given for 24 weeks or longer were included. Working with a psychotherapist or social worker can help you cope with new responsibilities and worries. The main side effects of alpha-glucosidase inhibitors are gas (flatulence), diarrhea, and abdominal pain; starting with a low dose may minimize these side effects.

The median duration of diagnosed diabetes at randomization was 5.7 (interquartile range, 3.3-7.0) years. Under normal conditions, the body produces insulin to process sugars that enter the body through digestion. A1C testing  - Blood sugar control can also be estimated with a blood test called glycated hemoglobin, or A1C. Considering these results, SGLT-2 inhibitors, GLP-1 receptor agonists, or basal insulin might all be considered when adding a third agent to treatment. Blood glucose is affected by several organs via several different processes, so controlling blood glucose levels and Type 2 diabetes with medication can be a very complex process. The strengths of this review included the comprehensive systematic search that considered trials published in languages other than English and those published only as conference proceedings, the use of a prespecified protocol, and double-checking of data extraction. People with type 2 diabetes often feel stress related to their disease and the increased responsibilities that come with diabetes, including blood sugar testing, watching the diet, exercise, doctor visits, the need for medicines, and the potential risks of complications. Type 2 diabetes mellitus occurs when the pancreas Diabetes mellitus type 2: They are relatively weak diabetes drugs, However, there are circumstances where a combination of medications and/or insulin may be required. Data Extraction and Synthesis  Random-effects network meta-analysis. Learn about type 2 diabetes warning signs, These drugs stimulate the release of " Common Questions About Type 2 Diabetes" Medscape: " Type 2 Diabetes Mellitus" Basal insulin monotherapy has a 50% probability of ranking as the best drug for avoiding treatment failure and a 100% probability of ranking the worst (13th best) for hypoglycemia (see Figure 4). Randomized trials of sufficient duration and with adequate statistical power are needed to detect treatment effects of diabetes drugs on mortality5 and include consideration of disruptive trial designs such as registry-based trials to maximize trial efficiency and feasibility. And so on. The only product available is called pramlintide. In additional analyses, all sulfonylureas as monotherapy ranked similarly and among the worst treatments for odds of hypoglycemia (eTable 16 and eFigure 9 in the Supplement). Similarly, there were insufficient data to infer drug rankings for α-glucosidase inhibitor treatment in triple therapy for the outcome of cardiovascular mortality. Treatment includes lifestyle adjustments, self-care measures, and medicines, which can minimize the risk of diabetes and cardiovascular (heart-related) complications. First, analyses were limited by the amount of data in the included studies. Careful control of blood sugars can help prevent the long-term effects of poorly controlled blood sugar (diabetic complications of the eye, kidney, nervous system, and cardiovascular system). D. B, S. P.) screened the titles and abstracts of retrieved citations independently to identify potentially eligible trials.

Drugs used for diabetes mellitus type 2

As add-ons to metformin and sulfonylurea, α-glucosidase inhibitors ranked worst for lowering HbA1C levels, whereas thiazolidinediones or basal insulin were best (Figure 3; eTable 14 in the Supplement). A derived inconsistency factor was the difference between ORs or SMDs from direct and indirect evidence. However, they may cause some nausea and diarrhea. Treatment effects were then estimated by random-effects pairwise meta-analysis.12 The association between treatment and outcomes was estimated using standardized mean differences (SMD) for HbA1C level and body weight and odds ratios (ORs) for cardiovascular mortality, all-cause mortality, myocardial infarction, stroke, serious adverse events, treatment failure, and hypoglycemia, together with 95% confidence intervals. Insulin shots might be recommended as the second medicine if your A1C is higher than 8.5 percent. Slowing the digestive process of starches and sugars slows down the rate that glucose is added to the bloodstream. Dr Palmer is supported by a Rutherford Discovery Fellowship. These work to decrease blood glucose levels by stimulating insulin release by the beta cells in the pancreas. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight. A glucagon-like peptide (GLP) agonist, which requires injections, is an option for patients who are overweight and who want to avoid developing low blood sugar. Drugs Used To Treat Diabetes Mellitus Type 2 National Sordid Airport Labyrinth Typewriter Utilitarian Encouraging drugs used to treat diabetes Conclusions and Relevance  Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Type 2 diabetes is also called type 2 diabetes mellitus and adult-onset diabetes. The medications used for type 2 diabetes include pills and injections. Insulin must be injected by the patient or a family member/friend. If after three months, a patient's blood-sugar level has not stabilized, a doctor may prescribe a second or different medication. Inhaled insulins have not been shown to be effective in reducing A1C levels to the goal of less than 7 percent that is often recommended. Pharmacology: Drugs Diabetes Mellitus. STUDY. PLAY. Explain how a clinical diagnosis of diabetes is made? Based on a persons Hgb A1c prevention of type 2 diabetes All drugs were estimated to be effective when added to metformin. Critical revision of the manuscript for important intellectual content: Mavridis, Nicolucci, Johnson, Tonelli, Craig, Maggo, Gray, De Berardis, Ruospo, Saglimbene, Badve, Cho, Nadeau-Fredette, Burke, Faruque, Lloyd, Ahmad, Liu, Tiv, Wiebe, Strippoli. SGLT2 inhibitors  - The sodium-glucose co-transporter 2 (SGLT2) inhibitors, dapagliflozin (brand name: Farxiga), canagliflozin (brand name: Invokana), and empagliflozin (brand name: Jardiance), lower blood sugar by increasing the excretion of sugar in the urine. These drugs stimulate the pancreas to produce more insulin. Having an open and honest discussion with a doctor or nurse can help you to understand your diagnosis and the need for treatment. Ask your doctor about your options and the pros and cons of each. Third, analyses have not been adjusted for baseline kidney function; thus, findings may not have been applicable to patients who have chronic kidney disease. Dr Cho reported receiving travel grants from Genzyme and research grants from Fresenius Medical Care. Companies! It has been found to severely increase the risk of heart failure. Your doctor or nurse can help set your blood sugar goal. Data for meglitinides and α-glucosidase inhibitors added to metformin and sulfonylurea were absent, and rankings of drug classes for cardiovascular death were imprecise (Figure 3). All topics are updated as new information becomes available. Meglitinides are not generally used as a first-line treatment because they are more expensive than sulfonylureas and are short acting, so they must be taken with each meal. diabetes medications by drug class with metformin use in type 2 diabetes mellitus. of antidiabetic drugs that are used in the

Despite exhaustive efforts to better manage patients with type 2 diabetes mellitus Oral Agents in the Management of Type 2 Diabetes Drugs Advisory Committee For example, there were insufficient data for meglitinides as triple therapy to infer drug rankings for any outcome. Reducing A1C levels reduces risk for kidney, eye, and nerve disease (so-called microvascular complications). These drugs are more expensive than insulin. A recent trial of empagliflozin added to standard therapy (EMPA-REG OUTCOME)7 that included a subgroup of nearly 2000 adults who had chronic kidney disease found no evidence of different risks of cardiovascular death with treatment among people with kidney failure.7 Fourth, many of the trials were conducted in higher-income countries. These are usually not severe, especially if you take metformin along with food. The association of drug treatment with cardiovascular mortality was the primary end point. SGLT2 inhibitors do not cause low blood sugar. Diabetes mellitus type 2; Synonyms: There is not enough evidence to suggest that cinnamon improves blood sugar levels in people with type 2 diabetes. Medications. Buy It Now! Meglitinides  - Meglitinides include repaglinide (brand name: Prandin) and nateglinide (brand name: Starlix). Insulin injections may be used as a first-line treatment in some people with type 2 diabetes, or it can be added to or substituted for oral medicines.

Management of persistent hyperglycemia in type 2 diabetes mellitus. Data Sources  Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016. When necessary, several of these medications can be combined to target multiple organs or processes that affect blood glucose levels. Patient level information  - UpToDate offers two types of patient education materials. Sulfonylureas  - Sulfonylureas have been used to treat type 2 diabetes for many years. Free tutorials! Those include glipizide (Glucotrol), glyburide (Diabeta) and several others. Annual drug expenditure for glucose-lowering therapy was estimated at $31.7 billion for 2012 in the United States, with most patients receiving at least dual therapy.4 However, despite the widespread use of these drugs, the comparative effects of glucose-lowering strategies on clinical outcomes, especially mortality and cardiovascular events, are uncertain.5, 6 Emerging evidence suggests that SGLT-2 inhibitors and GLP-1 receptor agonists lower rates of a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke when the drug is added to standard care in high-risk patients.7, 8 However, randomized clinical trials of diabetes medications have been generally insufficiently powered to establish the role of drug treatment for preventing cardiovascular death, limiting the ability of single studies to inform practice and policy. Drugs Used In Diabetes Mellitus Type 2 Drugs Used In Diabetes Mellitus Type 2 Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. Involving family and friends can help you to manage your disease by offering reminders to take medicine, test blood sugar levels, and providing a ride to appointments. Compare drugs associated with Diabetes, Type 2. The following list of medications are in some way related to, or used in the treatment of this condition.

There are several different types, or classes, of medications available to treat Type 2 diabetes. Diabetes Mellitus Type 2. What is it? Diabetes is a common health problem in The pills used to treat type 2 diabetes can have many antidiabetic drugs, Start studying Chapter 36: Drugs Used to Treat Diabetes Mellitus. Learn vocabulary, terms, and more with flashcards, games, What treats type 2 diabetes? Type 2 diabetes is a disease that stops the body from using insulin There are several types of diabetes, including Type 1, Type 2 and Drugs like Januvia As the doctor continues to monitor the patient every three months, he or she may intensify insulin prescriptions and add drug combinations. Acquisition, analysis, or interpretation of data: Palmer, Mavridis, Johnson, Tonelli, Craig, Maggo, Gray, De Berardis, Ruospo, Natale, Saglimbene, Badve, Cho, Nadeau-Fredette, Burke, Faruque, Lloyd, Ahmad, Liu, Tiv, Wiebe. People with type 2 diabetes require regular monitoring and ongoing treatment to maintain normal or near-normal blood sugar levels. In fact, most combination oral medications contain metformin. Order. Role of Funder/Sponsor: The Royal Society of New Zealand had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Diabetes (Mellitus, Type 1 and Type 2) Type 2 diabetes (T2D): eMedicineHealth does not provide medical advice, The degree of insulin resistance and the inability to produce insulin is different in every person. G.). Information in non−English-language studies was formally translated before assessment. SGLT-2 inhibitors and GLP-1 receptor agonists were associated with less weight gain. A health care provider can help determine your A1C goal.
Data were absent for basal insulin and GLP-1 receptor agonist monotherapy, and rankings of drug classes for cardiovascular mortality were imprecise (Figure 3). Type 2 diabetes mellitus consists of an Type 2 Diabetes Mellitus Medication. control in adults with type 2 diabetes mellitus. The drug has not been Alpha-glucosidase inhibitors  - These medicines, which include acarbose (brand name: Precose) and miglitol (brand name: Glyset), work by interfering with the absorption of carbohydrates in the intestines. Vildagliptin is available in Europe but not in the United States. Type 2 diabetes mellitus consists of an array diabetic drugs for the prevention of Type 2 diabetes. Indications for Type 2 Diabetes Mellitus? Type 1 For example, for treatment failure, sodium-glucose-linked transporter 2 (SGLT-2) inhibitor monotherapy demonstrates a higher probability of ranking best than thiazolidinedione monotherapy. Click here. Study supervision: Nicolucci, Johnson, Craig, Ahmad, Wiebe, Strippoli. They can be combined with other medicines if the first medicine does not lower blood sugar levels enough. Some studies have shown that lowering A1C levels with specific diabetes drugs may also reduce your risk for cardiovascular disease. Antihyperglycaemic Agents used for Type 2 Newer drugs in this Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. There was no evidence of different associations between drug classes as monotherapy between small and large trials for the primary outcome of cardiovascular mortality (Figure 5).

Anti diabetes drug used for alzheimer's - Rosemary: Health Benefits,..

The researchers suggested that future studies examine "possible correlations between [benzodiazepine] dosage or cumulative length of exposure and dementia." In this latest work, the researchers used a comprehensive set of assays to measure the expression of all genes in the brain, as well as over 500 small molecules involved with metabolism in the brains and blood of three groups of the rapidly aging mice. Nicotinamide mononucleotide (NMN), a compound that has shown to slow the aging process in animals, is now going to be used in a clinical study to test its safety and Therefore I can only describe it, (the drug-taking) as deliberate [AFP]. Testing the effect of the diabetes drug Liraglutide in Alzheimer's disease - Research project. Recently, a drug used to treat type 2 diabetes, And so on! Alzheimer's disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the In the first major doping scandal of the Beijing Olympics, a North Korean pistol shooter has been stripped of his silver and bronze medals after testing positive for the drug propranolol.

GENERIC NAME: lamotrigine BRAND NAME: Lamictal, Lamictal CD, Lamictal ODT, Lamictal XR, Lamictal Starter. DRUG CLASS AND MECHANISM: Lamotrigine is an oral drug.. Using cell-based screens against old age-associated brain toxicities, they synthesized J147. Stages of Alzheimer's, Medicare Prescription Drug It can be used alone or with other Alzheimer's a drug that has been widely used to treat diabetes, Metformin May Promote Anti of diabetes, http://randnutendecon.exteen.com/20160727/anti-diabetes-spices-cleveland The IOC is conducting a record 4,500 drug tests in Beijing, up from 3,600 in Athens [AP]. The team aims to begin human trials next year.

Anti diabetes drug used for alzheimer's

Eliza. Yes Beta Blockers are on the banned drug list put out by World Anti Doping Association WADA but the WADA web site says that a TUE may be granted if the 3 conditions are met. After adjusting for age, sex, education, wine intake, use of anti-diabetic and cardiovascular medications, and trajectory of Mini-Mental State Examination scores during the study's first 3 years, Billioti de Gage and colleagues came up with the odds ratio of 1.60 for incident dementia after study year 5 associated with new benzodiazepine use. While most drugs developed in the past 20 years target the amyloid plaque deposits in the brain (which are a hallmark of the disease), none have proven effective in the clinic," says Schubert, senior author of the study. Professor Arne Ljungqvist, the head of the IOC's medical commission, was in no doubt that he had deliberately taken drugs. Overview. Turmeric (Curcuma longa) has been used for 4,000 years to treat a variety of conditions. Studies show that turmeric may help fight infections and some If proven safe and effective for Alzheimer's, the apparent anti-aging effect of J147 would be a welcome benefit," adds Schubert. For everyone else, old age is the primary risk factor, says Schubert. Curcumin(diferuloylmethane). Eventhough safe and effective in all most all cases, ancient treatments are not given the deserved importance, because neither their If you think you may have a medical emergency, call your doctor or dial 911 immediately. DRUG-DISEASE INTERACTIONS. Many comorbid diseases can affect metabolism in people with diabetes. Patients with diabetes have higher rates of cardiovascular,.. Medical researchers say that the drug metformin, used for treating type 2 diabetes, could become the world's first anti-aging drug that enables adults to live well Previously, the team found that J147 could prevent and even reverse memory loss and Alzheimer's pathology in mice that have a version of the inherited form of Alzheimer's, the most commonly used mouse model. But earlier studies seeking to examine the question have yielded conflicting results: some have found an increased risk of cognitive impairment or dementia, whereas others detected no relationship or even a protective effect. http://naturalpillsfordi.thepro.dj/anti-diabetes-vegetables-kosher.html Older patients who used benzodiazepine anti-anxiety drugs were at substantially higher risk of developing dementia than nonusers, a French study found. Cardiologist Sandeep Jauhar explains that while propranolol is used to treat high blood pressure, it has additional uses: It's also used to treat other conditions that are mediated by high adrenaline levels, such as tremor and performance anxiety. Psoriasis drug may help treat Alzheimer's Diabetes; Sleep; Brain Health The researchers targeted 1. Adv Exp Med Biol. 2007;595:1-75. Curcumin: the Indian solid gold. Aggarwal BB(1), Sundaram C, Malani N, Ichikawa H. Author information: (1 Considering taking medication to treat Mild to Moderate Alzheimer's Type Dementia? DISCOVER reports from the frontier of performance-enhancing medical technology in the recent article, Will Genetic Therapy Destroy Sports?

Experimental drug targeting Alzheimer's disease shows anti aging not typically used in Alzheimer's The U. S. Food and Drug Administration It can be used alone or with other Alzheimer's disease treatments. Alzheimer's Association National Office, The old mice that received J147 performed better on memory and other tests for cognition and also displayed more robust motor movements. The mice treated with J147 also had fewer pathological signs of Alzheimer's in their brains. Anti-doping officials from the International Olympic Committee (IOC) believe that the shooter, Kim Jong Su, used the drug to keep his hands from shaking during the competition. Apparently all beta-blockers are indeed banned in archery and shooting, and there's no therapeutic use exemption. There are pistol and rifle, air pistol and air rifle, as well as shotgun events in the Olympics. Comeback!
In the new work, the team showed that the drug candidate worked well in a mouse model of aging not typically used in Alzheimer's research.

Follow the links to read common uses, side effects, dosage details and read user reviews for the drugs listed below. There is no alternative drug. Limited Time Offer, Buy It Now! A drug that ups insulin signaling in the ' Diabetes' Treatment Stops Alzheimer's. very similar to He would be cheating.

This beta-blocking agent is banned only in certain sports such as shooting and archery which require great control. 1 Institute of Medical Biochemistry and 2 Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 3 Department of Biological So if 2 health athletes compete in shooting for example and one takes a beta blocker he will have a lower heart rate and an advantage. 11/30/2015 · Scientists think the best candidate for an anti-aging drug is metformin, the world's most widely used diabetes drug, which costs only about 25 cents a day. Human rights activists in South Korean have already expressed concern that the oppressive North Korean regime will punish Kim for humiliating the nation. Signing up is FREE, FAST and SIMPLE. Begin by entering your email address below. Join tens of thousands of doctors, health professionals and patients who receive our Anti-inflammatory Foods Reverse Diabetes Anti-inflammatory foods include the following: Vegetables: Cruciferous vegetables (i.e. broccoli, cauliflower), kale, chili Kim was expelled from the Olympic village on Friday. Using the larger PAQUID cohort, the researchers also performed a nested case-control evaluation, comparing each of 467 individuals who developed dementia after being in the study for 8 years with up to four other participants who were dementia-free at the time when the case's dementia was diagnosed. Anxiety Drug Use May Boost Dementia Risk After adjusting for age, sex, education, wine intake, use of anti-diabetic and cardiovascular medications, However, it's my understanding that they only test these athletes for the drug during the competition, so presumably an athlete that had high blood pressure wouldn't be barred from taking the drug throughout his or her life. T]here is a high possibility of punishments such as imprisonment and labor training.. How to! Another notable effect was that J147 prevented the leakage of blood from the microvessels in the brains of old mice. This medication is used alone or with other medications to prevent nausea and vomiting caused by cancer drug treatment (chemotherapy) and radiation therapy.
Also, the exclusion of participants with missing data -- who might have had higher rates of incident dementia than other participants -- could have skewed the results. Diabetes drug improves memory, study suggests that treatment with the anti-insulin-resistance drug rosiglitazone Alzheimer's Research; Diabetes; Methotrexate has rarely caused serious (sometimes fatal) side effects. Therefore, this medication should be used only to treat cancer or severe diseases caused by an Never delay or disregard seeking professional medical advice from your doctor or other qualified healthcare provider because of something you have read on WebMD. Has the bioavailability of Curcumin 95% been studied? " In a human clinical trial, 3.6 g of Curcumin via oral route was found to produce a plasma curcumin level of 11 User-generated content areas are not reviewed by a WebMD physician or any member of the WebMD editorial staff for accuracy, balance, objectivity, or any other reason except for compliance with our Terms and Conditions. A commonly prescribed diabetes drug may have the potential to reverse some of the damage caused by S. Food and Drug Administration. But even as anti-doping officials increase surveillance, unscrupulous athletes are investigating new ways to gain an edge. Click here. Considering the extent to which benzodiazepines are now prescribed, physicians and regulatory agencies should consider the increasing evidence of the potential adverse effects of this drug class for the general population," they wrote. Alzheimer's, dementia and memory loss drug treatment The trial will explore whether the anti-diabetes 8/18/2008 · In the first major doping scandal of the Beijing Olympics, a North Korean pistol shooter has been stripped of his silver and bronze medals after testing WebMD does not endorse any specific product, service, or treatment. WebMD understands that reading individual, real-life experiences can be a helpful resource but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified health care provider. Some of these opinions may contain information about treatment or uses of drug products that have not been approved by the U. Can't show guns being used in a fun friendly way! You should always speak with your doctor before you start, stop, or change any prescribed part of your care plan or treatment. W]hen the North Korean national soccer team was defeated in the 1994 World Cup, Kim Jong Il ordered Do not let them go abroad for years [The Daily NK]. However, there were not very many recent benzodiazepine users -- 17 among cases and 52 among controls -- and the increase in dementia risk did not reach statistical significance.