This content was published in 2013. We do not recommend that you take any clinical decisions based on this information without first ensuring you have checked the latest guidance.
Metformin has a large evidence base for reducing both morbidity and mortality and it is, rightfully, first-line therapy in the treatment of type 2 diabetes. This is recommended not only by the National Institute for Health and Care Excellence, but also the American Diabetes Association and the European Association for the Study of Diabetes. Metformin lowers plasma glucose via four mechanisms. It:
- Reduces hepatic glucose production
- Increases insulin sensitivity in skeletal muscle
- Improves peripheral glucose uptake and usage
- Delays glucose absorption in the gastrointestinal tract
Importantly, metformin does not stimulate insulin secretion so although there is a small risk of hypoglycaemia if taken without food, this is minimal compared with other antidiabetic drugs. Metformin can, however, increase the risk of hypoglycaemia if used in combination with other antidiabetic medicines.
The mechanisms above mean that metformin predominantly increases insulin efficacy and so should be taken with meals when endogenous insulin is produced.
Gastrointestinal side effects with metformin — especially diarrhoea and nausea — are widely recognised. To minimise them, patients can be advised to take their tablets after meals rather than before and the dose should be titrated slowly, over a period of weeks. Frequently these side effects are most noticeable in the first few weeks after initiation. If patients are forewarned of side effects and told about the excellent benefits of metformin they are often more likely to keep going with medication for at least a month or two to see if they can cope.
For most people, three-times-a-day dosing is used to maximise efficiency (ie, because they eat three times a day, there is a reduction of resistance when insulin is most needed) but, as seen here, it can be inconvenient for patients and, in practice, I regularly see the lunchtime dose either being forgotten or being purposely omitted. As a result, metformin is now commonly prescribed in a twice daily dose, taken with the two largest meals of the day and not necessarily with breakfast and the evening meal. This dosing allows higher doses (eg, 1g bd) and more convenience for the patient.
In terms of this patient, I would recommend a switch to twice-a-day dosing to the prescriber. The dose would depend on his blood glucose control but if this is under control I would recommend 500mg with the smaller meal and 1g with the largest. If control is poor there is the potential to titrate up to 1g bd.
I have also come across patients taking their metformin at bedtime. This is an unnecessary dose because without the presence of a meal there is only basal insulin action. It is well worth checking when exactly patients take their medicine.
Instilling the habit of taking metformin with meals can be of further benefit if a patient’s dose needs to be increased or another antidiabetic drug, such as a sulfonylurea, is added, because it may prevent future problems with adherence.
Modified-release metformin is used frequently in practice, commonly as a oncedaily dose. It is recommended by NICE, but only after an adequate trial of standard metformin where gastrointestinal intolerability prevents continuation of therapy.1The cost of this option must be considered; metformin MR 500mg costs £5.32 for 56 tablets, while standard metformin 500mg costs £1.80 for 56. In the current health economy it would be a benefit to maintain as many patients as possible on standard metformin and slow titration of the dose can help achieve this. If a patient cannot tolerate side effects, modifiedrelease metformin would be preferable to changing to a different medicine (eg, a sulfonylurea, DPP4 inhibitor, a thiazolidinedione or insulin) —these should usually be reserved for when therapy needs to be stepped up because they come with their own risks, particularly hypoglycaemia.
In this case, where the patient is at an early treatment stage, it would be better to encourage him to take his metformin (possibly at an adjusted dose after talking to the prescriber) rather than recommend a move to an alternative class of drug. We do not know his current HbA1c and, therefore, do not know how good or bad his long-term blood glucose control is. Without this information it would be pre-emptive and probably ill considered to recommend an alternative.
There is technically no biological reason for people to eat three meals a day, although culturally this is the norm. However regular meals are recommended in diabetes as a way of minimising fluctuations in blood glucose levels because extreme hyperand hypoglycaemia have been shown to lead to poorer long-term outcomes.
A Cochrane review found that there was limited evidence for any particular diet and that regular exercise had the most benefit in lowering HbA1c. Regular small meals have also been linked to a reduced risk of obesity, although this has not been proven conclusively. However a study monitoring molecular changes related to meal frequency demonstrated that eating one large meal a day versus three smaller meals increases insulin resistance and glucose intolerance, which would best be avoided in diabetes patients.
Recent media interest has been focused on alternate day fasting. This diet involves eating without restrictions on one day, then a highly restricted diet (fewer than 600 calories a day for men and 500 calories for women) on the next. This is a way of reducing calories overall and a 10-week trial found that this was a viable diet option to help obese patients lose weight and lessen the risk of developing coronary artery disease. However, this diet has not been trialled in patients with diabetes. Moreover, it would have implications for therapy. For example, do patients still take medicines on fasting days? This is especially relevant in patients who are on insulin or sulfonylureas, where medication without food can lead to dangerous hypoglycaemia. Patients who are solely maintained on metformin are more likely to be able to cope with variable diets but these should not be undertaken without discussion with their healthcare team.
Weight loss is often a key focus in type 2 diabetes and a balanced low-fat, low-salt diet should be encouraged. NICE recommends a diet high in fibre, fruit and vegetables with a low glycaemic index and low in saturated fat.1 Carbohydrate counting and a low glycaemic index (GI) diet are often recommended by dietitians. Carbohydrate counting is predominantly used in patients with type 1 diabetes or those wit h type 2 diabetes treated with insulin. It may seem a little premature in those treated only with metformin but carbohydrate awareness may help patients to better understand their diets and identify areas for improvement.
A low GI diet is also a sensible recommendation but patients need to understand the limitations of relying on this measure and that it does not necessarily indicate that a food is healthy. For example, the presence of fat lowers GI values so a bag of crisps may have a lower GI value than boiled potatoes. Patients keen to adopt this diet should also be educated about the importance of maintaining a low -fat diet (people with diabetes do not metabolise fats properly and have an increased cardiovascular risk) and of ensuring that they eat a balance of carbohydrate, fat and protein.
Maintaining a healthy, well balanced diet is the key recommendation for patients, but a pragmatic approach must be taken. Although we may want patients to follow dietary advice this is not always possible and those who work shifts or who have irregular meal patterns should be counselled to take their metformin when they have a meal, regardless of the time of that meal.
Bear in mind that snacking can cause issues, especially if high-fat or high-sugar snacks are selected. It might be useful to explore with patients the reasons for missing meals. For example, if our patient tends to have a couple of breaks for snacks, he might be able to take one longer break instead. Or if he snacks because it is easier to grab a biscuit than make a sandwich, a conversation about food choices and timing might help. Diabetes UK offers a balanced view on a range of dietary questions including on low GI diets and fasting for Ramadan.
This patient could be encouraged to have a well balanced meal (and to take his metformin) just before he starts a shift and another when he finishes.
Patients’ fears about their diabetes affecting their employment status should be taken seriously. In this instance these are already affecting this patient’s treatment, causing him to miss meals and medication, and the potential problems could worsen if his treatment is altered.
The Equality Act 2010 brings together and extends existing antidiscrimination legislation, and pharmacists should be aware of it. Part of the Act’s purpose is to prevent discrimination because of, or arising from a disability, including discrimination by employers. Although diabetes is not considered by most people as a disability, workers with diabetes will be protected under the act, which defines disability as a physical or mental impairment that has a substantial and long-term adverse effect on a person’s ability to carry out normal day-to-day activities. However, it is important to note that other factors may affect a patient’s ability to carry out his or her job. Hypoglycaemia in the workplace is a serious consideration, both for the health of patients and their colleagues, particularly where activities such as driving or operating heavy machinery are involved. Ideally, patients should discuss their diabetes with their employer, occupational therapy department or human resources. Some employers may not be insured if an employee has not declared his or her condition and so are keen to be told at the earliest opportunity. This patient should be encouraged to discuss his condition, with reassurance that it should not affect his employability — it may mean that he finds it easier to manage his condition because his employer may endeavour to ensure he gets enough time to eat a meal rather than snacks.
Patient concerns about stigma should be discussed as appropriate. Although patients do not have to tell their colleagues about their condition, they could turn out to be a source of support and encouragement. It may be worth recommending patients join a local support group or read the Diabetes UK “Employment and diabetes” leaflet, which offers sensible advice.
There are a number of considerations here to take away. For this patient, the three main points would be:
- Take metformin only with meals.
- Try to stick to a balanced diet and eat as regularly as possible, avoiding high-sugar and high fat snacks.
- Speak to someone you trust at work to gain support.
- Metformin prescribed twice a day should, ideally, be taken with the two largest meals of the day.
- It is well worth asking patients when exactly they take their metformin because not all will be taking it with meals.
- Modified-release metformin should be reserved for where gastrointestinal side effects with standard release metformin are unacceptable.
- Regular meals minimise fluctuations in blood glucose levels. The alternate day fasting diet has been shown to help with weight loss and reducing cardiovascular risk but has not been trialled in patients with diabetes.
- Patients with diabetes are protected from discrimination at work under the Equality Act 2010.