Adjusting medications
on a low-carb diet

As a reminder, this information is intended for doctors, not for the general public (full disclaimer). Discuss any changes in medication and relevant lifestyle changes with your doctor.

Carbohydrate restriction in the form of a low-carb diet is effective for lowering blood sugar, reversing diabetes and reducing blood pressure.1 However, without careful monitoring, low-carb diets can be victims of their own success, triggering symptomatic hypoglycemia or hypotension. Therefore, clinicians using carbohydrate restriction need to be proactive about preventing these complications.

There are two major classes of medications that often need to be reduced on a low-carb diet: blood glucose-lowering medications and blood pressure medications. Learn more in these sections:

Blood glucose lowering medications

When patients with type 2 diabetes start a low-carb diet, their blood glucose levels usually go down from day one, and these levels can keep dropping as weight loss continues and insulin resistance improves.2

As this happens, patients on blood glucose-lowering medications may need to reduce their medications to avoid hypoglycemia. It’s important for their doctor to know how to handle this situation. Hypoglycemia due to overdosing of blood glucose-lowering medications, especially insulin, is the biggest risk when starting a low-carb diet.3

Slightly high glucose is safer than too low

It is difficult to anticipate exactly how your patient’s blood sugar levels are going to respond to a reduction of carbohydrate intake. Blood glucose levels will usually go down immediately, on day one, and often by a lot.

Because of this uncertainty and because low blood sugar levels are far more dangerous in the short term, it’s safer to have your patients’ sugars run a little bit higher than the desired range for the initial few days to weeks.4 This is to avoid the risk of hypoglycemia.

Deprescribing

If your patient is on insulin or sulfonylureas – with a high risk of hypoglycemia – you should reduce your patients’ medications to initially target daily blood glucose levels between 145 to 200 mg/dL (between 8.0 and 11.1 mmol/L). Although there will be individual variation, we recommend stopping sulfonylureas and short-acting insulin, and we recommend reducing long-acting insulin by 33-50% (depending on baseline glucose control and the patient’s wishes regarding strict glucose control vs. fear of hypoglycemia).

Also consider that the more your patient lowers his or her intake of carbs, the larger the blood glucose-lowering effect can be. This means that if your patient used to eat 300 grams of carbs per day and begins eating 20 grams per day, the effect on glucose levels is likely to be very powerful.5

To summarize, here’s the recommended order of de-prescribing diabetes medications for patients with type 2 diabetes.

  1. (due to the risk of ketoacidosis, see below)
  2. (risk of hypoglycemia)
  3. (risk of hypoglycemia)
  4. (risk of hypoglycemia)

You’ll find more details below.

Follow-up adjustments

Within the first few months, patients’ blood glucose levels commonly drop back down to an acceptable range. Once the patient’s levels are back into the 70-130 mg/dL range (4 to 7.0 mmol/L), it may be time to make medication reductions again, and again target a range of 145 to 200 mg/dL (8.0 to 11.1 mmol/L).6

This cycle can often repeat itself until the patient is no longer taking any diabetic medications (or is just on metformin). After that, the goal is to bring the glucose levels down to the normal range utilizing diet alone, targeting a normal HbA1c.

If there is no reduction in blood glucose levels between appointments, there does not need to be an adjustment. Talk to your patient about their diet. Perhaps they could make some adjustments to speed up the process, but sometimes it may just take a bit longer to see the glucose levels come down. If patients are slow to respond to a low-carb diet, put things in perspective by reminding them of how long they have had diabetes and how long it takes to develop.

Sometimes a patient’s blood glucose levels temporarily go above 200 mg/dL (11.1 mmol/L) for various reasons, such as a vacation, relatives visiting from out of town, illness or infection. If their sugars do not quickly normalize, that patient may need a short-term medication increase. Some patients may be resistant to this but assure them that it’s only for the short term and the goal is to reduce the dose as soon as is safe.

Reversal of type 2 diabetes7

It’s not uncommon for patients to fully reverse their type 2 diabetes on a strict low-carb diet. What does reversal mean? Reversal is defined as having a HbA1c measurement below 6.5% without medications except metformin, whereas remission of diabetes is defined as normoglycemia for at least 1 year, as indicated by at least two HbA1c measurements below 5.7% and no medications.8

More about type 2 diabetes medications

  

Medication Mechanism Pros and cons
SGLT-2 inhibitors

  • Invokana (canagliflozine)
  • Forxiga / Farxiga in the USA (dapagliflozine)
  • Jardiance (empagliflozine)
Inhibit type 2 sodium-glucose cotransporter.

Elimination of glucose in the urine, as reabsorption of glucose by the kidneys is reduced.

*** RISK OF DIABETIC KETO-ACIDOSIS *** especially on low carb, even if normal sugar levels. More reports with Invokana.

No risk of hypos.
No weight gain.
Possibly speed up reversal of T2D.*

Long-acting insulin

  • Lantus
  • Levemir
  • Toujeo
  • Tresiba
  • Basaglar
Forces cells to take in more glucose. High risk of getting hypos.
Increases weight gain.
Worsens insulin resistance.

Harder to titrate than short acting.
Intermediate and short-acting insulin

  • Humalog
  • NovoRapid
  • Apidra
  • Humulin R
  • Novolin ge Toronto
  • Humulin N
  • Novolin ge NPH
Forces cells to take in more glucose. High risk of getting hypos.
Increases weight gain.
Worsens insulin resistance.

Easier to titrate than long acting.
*Insulin LA+SA Combos: split back into long acting and short acting to better titrate
Sulfonylureas and Meglitinides

  • Diamicron (gliclazide)
  • Amaryl (glimepiride)
  • Diabeta (glyburide)
  • Starlix (nateglinide)
  • GlucoNorm (repaglinide)
Stimulate insulin secretion by the pancreas. Risk of hypos.
Weight gain.
DPP4 inhibitors

  • Januvia (sitagliptine)
  • Onglyza (saxagliptine)
  • Trajenta (linagliptine)
  • Nesina (alogliptine)
Prolong the action of GLP-1.
Stimulate the secretion of insulin.
Inhibit the release of glucagon.
No risk of hypos.
Not so useful if the patient is not eating a lot of carbs anymore.
GLP-1 agonists

  • Victoza (liraglutide)
  • Byetta (exenatide)
  • Eperzan (albiglutide)
  • Trulicity (dulaglutide)
Increase insulin production if blood sugar levels are high.
Decreases production of glucagon.
No risk of hypos.
Weight loss.
Reduced appetite, useful in that matter.
Alpha-glucosidase inhibitor

  • Glucobay (acarbose)
Inhibit last stage of glucose digestion.
Inhibit the transformation of starch into sugar.
Delay the absorption of certain types of carbs.
No risk of hypos.
No weight gain.
Few patients on this drug because it causes intestinal discomfort/diarrhoea.
Biguanides

  • Glucophage (metformin)
  • Glumetza (metformin)
Inhibit the production of glucose by the liver.
Decrease the absorption of glucose by the digestive system.
Increase the absorption of glucose in periphery.
No risk of hypos.
No weight gain.


 

A note on SGLT-2 inhibitors

Some doctors choose to have patients stay on SGLT-2 inhibitors and remove insulin and sulfonylureas first, when possible. This is because SGLT-2 inhibitors actively remove glucose from the body and thus reduce insulin levels. However, given the multiple case reports of euglycemic ketoacidosis with low- carb diets and SGLT-2 inhibitors, the risks of SGLT-2 inhibitors likely outweigh the benefits.9

Should you choose to continue with SGLT-2 therapy, please ask your patients to look out for the following early symptoms of ketoacidosis. They should stop taking the drug and notify you immediately if they develop:

  • Nausea
  • Weakness and fatigue
  • Dehydration

In most cases, however, and in the opinion of most doctors treating patients with low carb, SGLT-2 inhibitors may not be worth the risk of ketoacidosis. They should thus usually be removed first when starting a low-carb diet. This is based on clinical experience.

 

DPP4 vs. GLP-1

Discuss with your patient to see if they would prefer to reduce and discontinue their DDP4 inhibitors or GLP-1 agonists first.

  • Some people prefer to discontinue the GLP-1 agonist since it is an injectable and is inconvenient to use because it needs to be refrigerated.
  • However, others find that these injectables reduce their appetite, and they would prefer to reduce their DDP4 inhibitors first.

Since neither of these classes of medications put the patient at risk for hypoglycemia, it is really up to the patient’s preference. If the patient has no preference, start to reduce and discontinue the DPP4 inhibitors first, since the GLP-1 agonists may decrease hunger and cause some weight loss.
 

More resources

British Journal of General Practice 2018: Adapting diabetes medication for low carbohydrate management of type 2 diabetes: a practical guide 
 
One-page summary for clinicians: Type 2 diabetes medication reduction


Blood pressure medications

Baseline

Carbohydrate restriction is an effective way to lower blood pressure. However, the change happens more slowly than the change in blood sugar, potentially occurring within days or months. Therefore, you do not have to automatically adjust blood pressure medications as you need to with glucose-lowering medications.

Instead, this is something to assess during the follow-up. Start by making sure your patient is aware of potential symptoms of hypotension (such as experiencing dizziness, fatigue, or nausea) and knows to contact you immediately if they occur.

Follow-up

If the patient presents in clinic with low blood pressure or experiences low blood pressures at home, then you will likely need to reduce antihypertensive medications.

Determining what blood pressure medication to discontinue first

There isn’t a universal protocol of which drugs to stop first, as patients have different reasons for being on specific medicines, such as ACE inhibitors for those with diabetes, beta blockers for those with coronary disease, or alpha blockers for those with benign prostatic hypertrophy (BPH). Thus, we recommend individualizing the de-prescribing of anti-hypertensive medications.

However, if there is no alternative need for a medication, then we recommend stopping diuretics first, since low-carb diets frequently have a diuretic effect of their own.10

Instruct the patient to continue careful blood pressure monitoring to ensure there is no rebound increase once they reduce or stop their medications.

  1. For a comprehensive list of studies suporting this statement, see our guide on the science of low-carb and keto.

  2. Not only is this based on clinical experience, but multiple systemic reviews of RCTs suport this as well.

    Diabetes Research and Clinical Practice 2018: Effect of dietary carbohydrate restriction on glycemic control in adults with diabetes: A systematic review and meta-analysis [strong evidence]

    BMJ Open Diabetes Research and Care 2017: Systematic review and meta-analysis of dietary carbohydrate restriction in patients with type 2 diabetes [strong evidence]

    The American Journal of Clinical Nutrition 2018: Effects of low-carbohydrate- compared with low-fat-diet interventions on metabolic control in people with type 2 diabetes: a systematic review including GRADE assessments [strong evidence]

    Diabetes, Obesity & Metabolism 2019: An evidence‐based approach to developing low‐carbohydrate diets for type 2 diabetes management: a systematic review of interventions and methods [strong evidence]

  3. This is based on clinical experience of low-carb practitioners and was unanimously agreed upon by our low-carb expert panel. You can learn more about our panel here [weak evidence].

  4. This is based on clinical experience of low-carb practitioners and was unanimously agreed upon by our low-carb expert panel. You can learn more about our panel here [weak evidence].

  5. This is based on clinical experience of low-carb practitioners and was unanimously agreed upon by our low-carb expert panel. You can learn more about our panel here [weak evidence].

  6. This is based on clinical experience

  7. Some disagree with the use of the word “reverse” when it comes to type 2 diabetes. The concern is that it may imply the disease is completely gone, never to return. At Diet Doctor, we use the term “reverse” to indicate that the diagnosis of diabetes is no longer present at that moment. However, we acknowledge that the diagnosis of diabetes will likely return if a patient goes back to their prior high-carb eating habits. Therefore, “reverse” does not imply a forever cure.

  8. Diabetes Care 2009: How do we define cure of diabetes? [overview article; ungraded]

  9. Diabetes Care: Euglycemic diabetic ketoacidosis: A potential complication of treatment with sodium–glucose cotransporter 2 inhibition [case reports; very weak evidence]

    AACE Clinical Case Reports: Euglycemic diabetic ketoacidosis with SGLT2 inhibitor use in a patient on the Atkins diet: A unique presentation of a known side effect [case reports; very weak evidence]

  10. This is based on clinical experience