Category: Medical Info

Research and reports relating to diabetes.

Choosing medication in type two diabetes

kaitiscotland5 Comments

26_universita_di_bari

Cardiovascular Mortality of Diabetes Medications from Diabetes in Control

 

What should be the proper treatment selection for patients with type 2 diabetes?

The incidence of diabetes has been growing and the complications arising from uncontrolled blood glucose has been increasing along with it. It is estimated that more than 80% of deaths in developing countries are associated with life-threatening complications associated with diabetes.

Various treatment approaches have been implemented to avoid these complications and deaths related to diabetes. The mainstay of therapy for diabetes has been diet and exercise in conjunction with glucose-lowering drugs. Each of these agents are implicated with a potential benefit in health outcomes and mortality.

Agents from metformin have proven to be the first-line treatment due to its long-term benefits and improved glycemic control, to thiazolidinediones, which were falling out of favor due to their effects on heart failure and now proves to be beneficial in stroke.

Ongoing research efforts have compared various treatment modalities in head-to-head trials in order to understand glycemic events in diabetes. In a recent meta-analysis conducted by Giovanni F.M. Strippoli, PhD at the University of Bari, it is explained that sometimes these trials fail to dive into the cardiovascular mortality of these medications due to its inability to compare all treatment modalities simultaneously.

Strippoli and colleagues wanted to estimate the relative efficacy and safety of glucose-lowering medications. They extracted data from 301 clinical trials, which took into account 1,417,367 patient-months. All of these trials were 24 weeks of duration or longer. They included biguanides, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 agonists, basal insulin, meglitinides, and alpha-glucosidase inhibitors.

All of those studies that looked at medication regimens no longer supported by treatment guidelines or that have been withdrawn from the market were excluded from the study.

The primary endpoint of the study was the association of drug treatments with cardiovascular mortality.

Secondary endpoints were stratified into two endpoints, individual safety and individual efficacy. Secondary efficacy endpoints included all-cause mortality, myocardial infarction, stroke, A1c levels, and treatment failure.

Secondary safety endpoints included serious adverse events, hypoglycemia, and body weight.(My comment: the  pros and cons that patients and doctors are most interested in)

After randomization, trials were separated into those where patients were given a monotherapy regimen, other drugs were added to metformin, or where other drugs added to metformin and sulfonylureas.

In those trials where drugs were used as monotherapy, there was no significant difference in the drugs used as monotherapy and the odds of death from cardiovascular complications. Nonetheless, these were associated with lower A1c levels. However, there was insufficient data to determine treatment rankings for these effects.

There was a greater risk of hypoglycemia with basal insulin (OR, 17.9 [95% CI, 1.97 to 162]; RD, 10% [95% CI, 0.08% to 20%]) or sulfonylureas (OR, 3.13 [95% CI, 2.39 to 4.12]; RD, 10% [95% CI, 7% to 13%]) as monotherapy. Furthermore, when analyzing those drugs added to metformin there was no significant association between any drug classes and the risk of death, despite 45 cardiovascular deaths reported in 26 trials. Similar findings were seen in all-cause mortality and myocardial infarction when adding other drugs to metformin therapy. However, there was lower risk of stroke in those regimens that included metformin and DPP-4 inhibitors when compared to metformin and sulfonylureas (OR, 0.47 [95% CI, 0.23 to 0.95]; RD, −0.2% [95% CI, −0.4% to −0.04%).

Treatment failure was noted less often in those patients receiving metformin and SGLT-2 inhibitors. In terms of weight and hypoglycemia, the use of metformin and sulfonylureas ranked worse when compared to all different treatment modalities. Furthermore, in the third set of trials that looked at drugs added to metformin and sulfonylureas, there was no association between any of drugs and the risk of cardiovascular death. This same trend was seen with all-cause mortality and serious adverse events; no significant association was observed.

Alpha-glucosidase inhibitors provided the least A1c reduction when added to metformin and sulfonylureas, when compared to the implementation of basal insulin or thiazolidinediones (SMD, 1.42 [95% CI, 0.57 to 2.26]). Treatment failure was more notable in patients receiving DPP-4 inhibitors when compared to those patients where basal insulin was added. Hypoglycemia was observed less in those patients receiving GLP-1 agonists than those receiving thiazolidinediones. All drug classes provided weight reductions except thiazolidinediones and basal insulin.

In conclusion, these findings highlight that the use of glucose lowering agents alone or in combination are not implicated with cardiovascular mortality, all-cause mortality, or serious adverse events. Significant reductions in A1c can be obtained with the use of individual glucose lowering) agents. When these agents are added to metformin, clinically significant reductions can be obtained.

Practice Pearls:

  • Sulfonylureas or basal insulin should be avoided in the setting where hypoglycemia is of great concern.
  • Weight reductions can be obtained with regimens utilizing SGLT-2 inhibitors and GLP-1 agonists.
  • There is no significant association between the use of various glucose-lowering medications (alone or in combination) and the risk of cardiovascular mortality.

References:

Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis. JAMA. 2016;316(3):313-324. doi:10.1001/jama.2016.9400.

American Diabetes Association. Standards of medical care in diabetes: Summary of revisions-2016, 7: approaches to glycemic treatment. Diabetes Care. 2016;38(suppl):S4-S5

Gloomy news if you are overweight

kaitiscotland5 Comments
diabetes in cats
He’s a pudgy pussy – but may have a better chance than humans of getting slim again

Obese Have Low Chance of Recovering Normal Body Weight

From Diabetes in Control July 17th 2016

The chance of an obese person attaining normal body weight is 1 in 210 for men and 1 in 124 for women, increasing to 1 in 1,290 for men and 1 in 677 for women with severe obesity, according to a study of UK health records led by King’s College London. The findings suggest that current weight management programmes focused on dieting and exercise are not effective in tackling obesity at population level.

The research, funded by the National Institute for Health Research (NIHR), tracked the weight of 278,982 participants (129,194 men and 149,788) women using electronic health records from 2004 to 2014. The study looked at the probability of obese patients attaining normal weight or a 5% reduction in body weight; patients who received bariatric surgery were excluded from the study. A minimum of three body mass index (BMI) records per patient was used to estimate weight changes.

The annual chance of obese patients achieving five per cent weight loss was 1 in 12 for men and 1 in 10 for women. For those people who achieved five per cent weight loss, 53 per cent regained this weight within two years and 78 percent had regained the weight within five years.

Overall, only 1,283 men and 2,245 women with a BMI of 30-35 reached their normal body weight, equivalent to an annual probability of 1 in 210 for men and 1 in 124 for women; for those with a BMI above 40, the odds increased to 1 in 1,290 for men and 1 in 677 for women with severe obesity.

Weight cycling, with both increases and decreases in body weight, was also observed in more than a third of patients. The study concludes that current obesity treatments are failing to achieve sustained weight loss for the majority of obese patients.

Dr. Alison Fildes, first author from the Division of Health and Social Care Research at King’s College London (and now based at UCL), said: ‘Losing 5 to 10 per cent of your body weight has been shown to have meaningful health benefits and is often recommended as a weight loss target. These findings highlight how difficult it is for people with obesity to achieve and maintain even small amounts of weight loss.’

“The main treatment options offered to obese patients in the UK are weight management programmes accessed via their GP. This evidence suggests the current system is not working for the vast majority of obese patients.” “Once an adult becomes obese, it is very unlikely that they will return to a healthy body weight. New approaches are urgently needed to deal with this issue. Obesity treatments should focus on preventing overweight and obese patients gaining further weight, while also helping those that do lose weight to keep it off. More importantly, priority needs to be placed on preventing weight gain in the first place.”

Professor Martin Gulliford, senior author from the Division of Health and Social Care Research at King’s College London, said: “Current strategies to tackle obesity, which mainly focus on cutting calories and boosting physical activity, are failing to help the majority of obese patients to shed weight and maintain that weight loss. The greatest opportunity for stemming the current obesity epidemic is in wider-reaching public health policies to prevent obesity in the population.”

Kings College London News Release
Alison Fildes. American Journal of Public Health. Published online ahead of print July 16, 2015: e1–e6. doi:10.2105/AJPH.2015.302773

What do you do if you run out of insulin?

kaitiscotland3 Comments
type 1 diabetes medical equipment

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The predicament of having difficulty getting insulin if it runs out for any reason, shouldn’t be a disaster in the UK. We have the NHS and you can go to your regular Pharmacist, ANY Pharmacist, your own GP, ANY GP or ANY Accident and Emergency Department and get a prescription free of charge.  
This is NOT the situation in the USA and here is a “Disasters Averted” story published o  16 August 20016 which discusses the situation and possible options you can take if you live there or ever face problems in the country in which you live.
As always with diabetes it helps to know about your possible options before the worst happens. When travelling always carry double what you think you will need. Insulin MUST be taken on carry on luggage so it doesn’t freeze in the hold of a plane. Also split your medications and gear with a pal so that if one of you is robbed you have spares.
 
 Out  of Insulin, Too Early to Renew — What To Do?

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It is not unusual for people to have difficulty keeping insulin from freezing or getting overheated. A patient, with type 1 diabetes for 17 years, had glucose that did not respond to his rapid-acting insulin as it usually does. He had two new vials in the refrigerator. He took a new vial out of his refrigerator earlier in the day, and started using it a few hours after he took it out. Had high post prandials that did not respond as usual to correcting. He had enough experience to wonder if perhaps something was wrong with his new insulin, so he thought he’d try another vial. He saw it was frozen. He had put the two vials at the back, where for many refrigerators it is colder. He thought back and wondered if the first vial looked any different, but remembered, he did not look closely at it.

He then went to get a new prescription filled at his pharmacy, but was told insurance would not cover it at this date; it was too early. It was cost prohibitive for him to pay out of pocket ~$300.00/vial. He contacted a diabetes health care provider (hcp) who offered him two sample vials to cover him until his prescription would once again be covered. He corrected and his glucose lowered. Disaster averted!

Not everyone has the luxury of having a hcp who has samples available in such a timely manner. If their hcp even had them, what if it were a weekend, or another time that the hcp did not have access to the samples? I reached out to certified diabetes educator, Laurie Klipfel, RN, MSN, BC-ANP, CDE, to see if she could offer any pearls of wisdom:

“This was a recent discussion on an AADE list serve with many good suggestions. The best suggestion was asking the healthcare provider if samples were available.  My next option would be to see if the insurance would make an exception under the circumstances (but this may take time). Someone with type 1 needs their insulin and cannot wait a day or two. The next option is to see if a diabetes educator could contact a rep for samples (their prescribing healthcare provider would also need to be involved). My next option would be to see if there were coupons available online from websites like: www.rxpharmacycoupons.com, or other websites. As a last resort (but may be the fastest option in a pinch), if a patient was not able to afford the analog insulins such as Novolog, Humalog, or Apidra, I might suggest discussing with the healthcare provider if using regular insulin instead would be an option. Though the analogs match insulin need to insulin much better than regular insulin, taking regular insulin (especially when using a generic brand such as Walmart’s ReliOn brand) can be a much cheaper option and would be much better than not taking any meal dose insulin at all.  It would be beneficial to explain the differences in action times and suggest taking regular insulin 15-30 min. before the meal and beware of potential hypoglycemia 3-5 hours after injection due to longer action of regular. Of note, you do not need a prescription for regular, NPH or 70/30 insulin.

“I would also agree with suggestions made on the list serve for keeping the insulin in the door of the refrigerator and using a thermometer in the refrigerator. If the temperature in the refrigerator is not stable, it may be helpful to have the thermostat of the refrigerator checked.“

Lessons Learned:

 

    • People who have diabetes, especially type 1 diabetes, need to have and take insulin that is effective.
    • If you have type 1 diabetes, you are in danger of DKA. Know what it is, how to prevent, recognize, and get help for DKA.
    • A back-up plan for insulin gone bad or not available.
    • To double check insulin when taken out of the refrigerator for the “feel of the temperature” of the insulin. Do not use if hot, warm, or frozen.
    • To know what their insulin should look like, clear or cloudy. Avoid it if crystals, clumps or anything unusual is noted.
    • The onset, peak, and length of action of insulins they are taking, as well as replacements if needed.
    • If insulin is not available and can’t get insulin within hours, to visit the nearest ED or urgent care center.

Most people need a minimum of one hour exercise a day

kaitiscotland1 Comment

walking

How Much Exercise Compensates for Sitting at a Desk for eight Hours A Day?

Diabetes in Control August 27th 2016

At least an hour of physical activity needed to offset risk for several chronic conditions and mortality

Sedentary behavior has been associated with increased risk of several chronic conditions and mortality. However, it is unclear whether physical activity attenuates or even eliminates the detrimental effects of prolonged sitting. A new study examined the associations of sedentary behavior and physical activity with all-cause mortality.

The meta-analysis of trials involving more than 1 million individuals was reported online July 27 in The Lancet. It is one of a special series of papers on physical activity.

The Lancet notes that its first series on physical activity in 2012 concluded that, “physical inactivity is as important a modifiable risk factor for chronic diseases as obesity and tobacco.” The meta-analysis found that 1 hour of moderate-intensity activity, such as brisk walking or riding a bicycle, can offset the health risks of sitting for 8 hours a day. Twenty-five percent of all individuals in the study reported this level of physical activity. The study also discovered that even shorter periods of 25 minutes a day can be beneficial.

For those of us who work by sitting at a desk, it can be very difficult not to sit while we do our jobs.  But, there are still many ways to get moving, like going for a walk during lunch, or even getting up and walking over to an associate to hand them a note instead of sending an email.  There are many ways to get in your physical activity.

According to the researchers, the data from more than a million people is the first meta-analysis to use a harmonized approach to directly compare mortality between people with different levels of sitting time and physical activity. They included 16 studies, with data on 1,005,791 individuals (aged >45 years) from the United States, Western Europe, and Australia.

Researchers divided the study participants into four groups based on their reported levels of physical activity: <5 min/day; 25-35 min/day; 50-60 min/day; and 60-75 min/day.

Researchers noted that, “Among the most active, there was no significant relation between the amount of sitting and mortality rates, suggesting that high physical activity eliminated the increased risk of prolonged sitting on mortality.” But as the amount of physical activity decreased, the risk for premature death increased.

Researchers found prolonged sitting associated with an increase in all-cause mortality, mainly due to cardiovascular disease and cancer (breast, colon, and colorectal), noting that, “A clear dose-response association was observed, with an almost curvilinear augmented risk for all-cause mortality with increased sitting time in combination with lower levels of activity.”

Compared with the referent group (i.e., those sitting <4 h/day and in the most active quartile [>35·5 MET-h per week]), mortality rates during follow-up were 12–59% higher in the two lowest quartiles of physical activity (from HR=1·12, 95% CI 1·08–1·16, for the second lowest quartile of physical activity [<16 MET-h per week] and sitting <4 h/day; to HR=1·59, 1·52–1·66, for the lowest quartile of physical activity [<2·5 MET-h per week] and sitting >8 h/day). Daily sitting time was not associated with increased all-cause mortality in those in the most active quartile of physical activity. Compared with the referent (<4 h of sitting per day and highest quartile of physical activity [>35·5 MET-h per week]), there was no increased risk of mortality during follow-up in those who sat for more than 8 h/day but who also reported >35·5 MET-h per week of activity (HR=1·04; 95% CI 0·99–1·10). By contrast, those who sat the least (<4 h/day) and were in the lowest activity quartile (<2·5 MET-h per week) had a significantly increased risk of dying during follow-up (HR=1·27, 95% CI 1·22–1·31). Six studies had data on TV-viewing time (N=465 450; 43 740 deaths). Watching TV for 3 h or more per day was associated with increased mortality regardless of physical activity, except in the most active quartile, where mortality was significantly increased only in people who watched TV for 5 h/day or more (HR=1·16, 1·05–1·28).

In conclusion, the researchers emphasized that high levels of moderate intensity physical activity (i.e., about 60–75 min per day) seem to eliminate the increased risk of death associated with high sitting time. However, this high activity level attenuates, but does not eliminate the increased risk associated with high TV-viewing time. These results provide further evidence on the benefits of physical activity, particularly in societies where increasing numbers of people have to sit for long hours for work and may also inform future public health recommendations.

In another study published online by JAMA Ophthalmology in August, they found that sedentary behavior may be associated with diabetic retinopathy.  The analysis included 282 participants with diabetes. The average age was 62 years, 29 percent had mild or worse DR, and participants engaged in an average of 522 min/d of SB. The author found that for a 60-min/d increase in SB, participants had 16 percent increased odds of having mild or worse DR; total PA was not associated with DR.  “The plausibility of this positive association between SB and DR may in part be a result of the increased cardiovascular disease risks associated with SB, which in turn may increase the risk of DR.  In order to prove a cause and effect of SB and worsening DR s larger study would be needed.”

Practice Pearls

  • Inactivity is linked to a decreased production of certain hormones.
  • We need to break up periods of sitting for prolonged periods with short bursts of activity.
  • Walking 5 minutes every hour can offset sitting for the other 55 minutes per hour.

Lancet. Published online July 27, 2016. Abstract Editorial How Much Exercise Compensates for Sitting at a Desk Eight Hours A Day?#848 (1)]–[www_diabetesincontrol_com_how_]-[MTExNjQyNDI1NTE1S0]–

Over 60 with high LDL? : So what?

kaitiscotland3 Comments

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If you are over the age of 60 it’s time to stop fretting about your total cholesterol and low density cholesterol levels. Unless perhaps the levels are on the low side. Indeed total mortality rates are at least the same and usually better if your cholesterol levels are high.  Many doctors now believe it is the PATTERN of different lipid levels that is much more important, particularly high triglycerides and low HDL.

This systematic review tells the story:

Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review — Ravnskov et al. 6 (6) — BMJ Open

BMJ Open 2016;6:e010401 doi:10.1136/bmjopen-2015-010401

How does mental distress show physically?

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8558187594_65216d9621_bAlmost every patient with stress related mental health problems reports at least one somatic symptom and 45 per cent report six symptoms or more, according to a Swedish study of 228 patients suffering from what is termed as exhaustion disorder.

Here is the chart run down of the most common symptoms:

Almost all: Tiredness and low energy

67% Nausea, gas and indigestion

65% Headaches

57% Dizziness

Men and women reported the same number of symptoms.

Chest pain and sexual problems and pain during sex were more reported in men.

Pain in the arms, legs, joints, knees, hips reported more in the over 40s.

The more severe the mental health problem the higher the number of somatic symptoms.

From Human Givens Volume 21 No 1 2014

 

(BMC Psychiatry, 2014, 14, 118)

Although the causes of fibromyalgia are insufficiently understood at present and there is dubiety over whether the condition is due to stress or physical factors I have reproduced a chart which does show many psychosomatic symptoms in its presentation.

 

Symptoms_of_fibromyalgia.png

 

 

 

Health anxiety for diabetics is as bad as for neurological patients

kaitiscotland3 Comments

 

girl_suffering_from_anxiety

A quarter of Canadian diabetics, with either type one or two diabetes suffer from a tendency to worry about their health and thus misinterpret bodily sensations as more serious and threatening than they actually are.

Neurological patients have the same degree of anxiety, judged the highest for all patient groups.

Health anxiety was worse in younger patients, females, those recently diagnosed and those who were unmarried.

They had anxiety, a fear of diabetes complications, poorer adherence to dietary and self care activities and a lower physical quality of life.

The researches add, “The cognitive behavioural theory of health anxiety suggests than health anxiety increases when patients feel more vulnerable, perceive the medical condition to be more distressing, feel they are unable to cope with the medical condition, and believe that resources for coping with the medical condition are inadequate.”

From Human Givens Volume 21. No 1 2014

(Janzen Claude JA Hadjistavropoulos, HD and Friesen, L (2014) Exploration of health anxiety among individuals with diabetes: prevalence and implications, Journal of Health Psychology, 19,2 312-22)

Public Health Collaboration: Free booklets

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LA2-vx06-konsthallen-skulpturThis is the link to the Public Health Collaboration site where you can download for free or order print versions, at a modest cost, of illustrated health booklets that will help you:

 

know what to eat for a wide variety of good health outcomes

plan your meals

count your carbohydrates

lose fat

https://www.PHCuk.org/booklets/

 

Hopefully you will end up somewhere between the extremes of our sisters up there!

Influenza vaccine reduces total mortality in diabetics

kaitiscotland6 Comments

flu_shot_advertising

 

From Diabetes in Control

Could Influenza Vaccination Prevent More Than Just the Flu?

 

Currently, only low-quality evidence exists to support efficacy of influenza vaccination to prevent seasonal influenza in patients with diabetes. There is even less information regarding the impact of influenza vaccination on cardiovascular events or all-cause mortality in this population. A recent study published in the Canadian Medical Association Journal was designed to evaluate the impact of seasonal influenza vaccination on admission to the hospital for acute myocardial infarction, stroke, heart failure, or pneumonia, and all-cause mortality in patients with type 2 diabetes.

Conducted over a 7-year time period from 2003 – 2009, the study analyzed retrospective patient data from the Clinical Practice Research Datalink in England. The analysis included 124,503 adult patients diagnosed with type 2 diabetes. At baseline, characteristics such as age, sex, smoking status, BMI, cholesterol labs, HbA1c, blood pressure, medications, and comorbidities were compared between patient groups. Vaccination rates of the included participants ranged from 63.1% to 69.0% per year. In general, unvaccinated participants were younger, had lower rates of pre-existing comorbidities, and were taking fewer medications.

The baseline characteristics of subjects enrolled in this retrospective analysis showed that sicker subjects received the flu vaccination more frequently. Given this observation, and seasonal confounding of flu outbreaks, data adjustments favored fewer cardiovascular events and lower rates of all-cause mortality during the influenza season spanning 7 years of data.  While other studies have shown that influenza vaccination can reduce the risk of cardiovascular events in high-risk patients, this study is the first to demonstrate a reduction in cardiovascular events associated with influenza vaccination in patients with diabetes. This study is notable for its large sample size and long duration. However, given the retrospective nature of the study, further trials are warranted to offer conclusive evidence about the benefits of influenza vaccination in patients with diabetes.

Practice Pearls:

  • Previous clinical trials aimed at studying the effectiveness of the flu vaccine in patients with diabetes are often small, inconclusive, and have not investigated cardiovascular outcomes.
  • When data was adjusted for baseline covariates and seasonal residual confounding, patients who received the influenza vaccination had significantly reduced rates of hospital admissions for stroke, heart failure, pneumonia or influenza, and all-cause mortality.
  • Large experimental or quasi-experimental trials are needed to establish a causal link between influenza vaccination and clinical endpoints in patients with diabetes.

References:

Vamos EP, Pape UJ, Curcin V, Harris DPhil MJ, Valabhji J, Majeed A, et al.  Effectiveness of the Influenza vaccine in preventing admission to hospital and death in people with type 2 diabetes.  CMAJ. 2016 July 25.

Remschmidt C, Wichmann O, Harder T. Vaccines for the prevention of seasonal influenza in patients with diabetes: systematic review and meta-analysis. BMC Med 2015;13:53.

Researched and prepared by Alysa Redlich, Pharm.D. Candidate, University of Rhode Island, reviewed by Michelle Caetano, Pharm.D., BCPS, BCACP, CDOE, CVDOE

Could Metformin be useful to prevent Alzheimer’s?

kaitiscotland3 Comments

 

 

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From Diabetes in Control.
July 16th, 2016
The diabetes drug may have a beneficial effect on neurodegenerative diseases.
Metformin, a biguanide, is an oral diabetes medicine used to improve blood glucose levels in people with type 2 diabetes. There have been various studies on other uses of metformin. It may be beneficial in Alzheimer’s disease, stroke and other degenerative brain cell diseases. An animal study found that metformin helps neurogenesis and enhances hippocampus, a key pathway (aPKC-CBP).

Type 2 diabetes doubles the risk of having dementia; though some studies show metformin helps reduce risk, other studies show antidiabetic medications like insulin are linked to increased risk of having dementia.

Animal studies show that metformin recruits endogenous neural stem cells and also promotes the genesis of new neurons. Metformin, however, needs to have been used for a longer period before a drastic reduction in neurodegenerative disease and its neuroprotective nature is seen.
The purpose of this study is to find a link between antidiabetic medications, especially metformin and other neurodegenerative diseases. Also, to know how long one has to be on these antidiabetics before the neuroprotective nature kicks in.

A cohort study of type 2 diabetes patients who are 55 years and above and being managed on a monotherapy antidiabetic drug of either metformin, sulfonylurea (SU), thiazolidinedione (TZD) or insulin were observed in a period of 5 years.

In the course of 5 years, dementia was identified in 9.9% of the patients. Comparing those taking metformin to those taking sulfonylurea, there was a 20% reduction in dementia in those taking metformin. The hazard ratio 0.79%, a 95% confidence interval of 0.65-0.95.

For TZD, metformin had a 23% reduction in having dementia as compared to TZD with hazard ratio of 0.77, 95% confidence interval of 0.66-0.90.

Whereas those on SU as compared to metformin had a 24% increased risk for dementia with a hazard ratio of 1.24, 95% confidence interval of 1.1-1.4.TZD had an 18% increased risk, hazard ratio of 1.18, 95% confidence interval of 1.1-1.4.

Insulin had the highest risk of 28% with hazard ratio of 1.28, 95% confidence interval of 1.1-1.6.

These findings proved that metformin use has neuroprotective benefits while insulin has an increased risk of one having dementia.
In yet another study, patients 50 years and older from Veterans Affairs, diagnosed with type 2 diabetes, were recruited. Those on insulin were followed from the time they started insulin. The exclusion criteria were neuropathy, vitamin B12 deficiency, cognitive impairment, cerebrovascular disease, renal disease, and those who took insulin for less than two thirds of the study period. The sample size after all exclusions was 6,046 patients with 90% of them being male and a median age of 5.25 years.

334 cases of dementia were diagnosed, 100 of them had Parkinson’s, 71 had Alzheimer’s disease and 19 had cognitive impairment during the follow up period. The incidence of developing neurodegenerative disease was lower (2.08) for those who never used metformin as against those who used it for less than a year, which was (2.47). Metformin usage for 4 years was 0.49, 2 to 4 years was 1.30 and 1.61 for less than 2 years. This proves that the longer one stays on metformin the better the neuroprotective benefits take effect.

This study was significant for dementia (0.567 at 2-4 years and 0.252 for more than 4 years), but for Parkinson’s and Alzheimer’s disease it was 0.038 and 0.229 respectively, which happened from four years and beyond. For future studies, a larger scale prospective cohort study is needed to approve the connection between metformin use and the risk for neurodegenerative disease.

A spatial learning maze test performed on mice showed those given metformin (200mg/kg) were significantly better to be able to learn the location of a submerged platform as compared to those given a sterile saline solution.

Other studies have also proposed that metformin could stimulate neurogenesis from human neural stem cells.
Metformin is known to cross the blood-brain barrier, and has pleiotropic effects. It is known to have other possible preventive roles in cancer and heart disease. From all these various studies, one can conclude that metformin does have a therapeutic potential for mild cognitive impairment and dementia.
Practice Pearls:
Metformin use for more than 2 years has a significant reduction in neurodegenerative disease; it is neuroprotective as well as promoting neurogenesis.
Though the mechanism between metformin and neurodegenerative disease is uncertain, it is known to cross the blood brain barrier and has pleiotropic effects.
Growing evidence suggests that neural stem cells play a role in the repair of injuries or a degenerated brain.

Shi Qian, Lui Shuqian, Foseca Vivian, et al. “The effort of Metformin Exposure on Neurodegenerative disease among Elder Adult Veterans with Diabetes Mellitus”. American Diabetes Association-76th Scientific session 2016. Web June 19 2016.
Wang Jing, et al. “Metformin Activates an Atypical PKC-CBP Pathway to promote Neurogenesis and Enhance Spatial Memory Formation”. Cell Stem Cell. Vol 11(1) July 2012. Web June 19 2016.
Knopman David S et al. “Metformin Cuts Dementia Risk in Type 2 Diabetes”. Alzheimer Association International. July 2013. Web 19 2016.