Trulicity® and low blood sugar

Table 3: the US placebo-controlled trials

The US label counts two things: any episode with glucose below 54 mg/dL, with or without symptoms, and severe hypoglycemia, where another person had to give carbohydrate, glucagon or other emergency help. ^[1] Each row is a separate trial with its own background medicines and length, so the rows cannot be added together.

Longer trials and the higher doses

• Sulfonylurea, 78 weeks: readings below 54 mg/dL in 20% on 0.75 mg and 21% on 1.5 mg; severe episodes in 0% and 0.7%. ^[1]
• Mealtime (prandial) insulin, 52 weeks: 77% on 0.75 mg and 69% on 1.5 mg; severe episodes in 2.7% and 3.4%. ^[1]
• 1.5 mg, 3 mg and 4.5 mg with metformin, 36 weeks: 1.1%, 0.3% and 1.1%; severe episodes in 0.2%, 0% and 0.2%. Going up to 4.5 mg did not change the picture much in that setting. ^[1]
• Section 5.3 explains the pattern: a sulfonylurea or insulin can lower glucose by itself, and adding Trulicity® can raise that risk, including severe lows. ^[1]

Europe and Canada use a different yardstick

The EU summary and the Canadian monograph report “documented symptomatic” hypoglycemia: symptoms plus a measured glucose of 3.9 mmol/L or less. ^[3][4] That is about 70 mg/dL, the level MedlinePlus calls low, whereas the US figure starts at 54 mg/dL (3.0 mmol/L), a level MedlinePlus says can bring on more severe symptoms. ^[7] A higher threshold catches milder lows, so the European and Canadian percentages are larger even when they describe the same trials. The US and Canadian documents define a severe episode in the same way, as one needing another person’s help. ^[1][4]

Europe sorts the results into frequency classes. Hypoglycemia is “very common” (more than 1 in 10) when Trulicity® is used with insulin, glimepiride, or metformin plus glimepiride, and “common” (up to 1 in 10) when it is used alone or with metformin and pioglitazone; with metformin alone it is very common on 1.5 mg and common on 0.75 mg. ^[3] The EU leaflet also lists it as common with an SGLT2 inhibitor. ^[3]

What two published trials add

AWARD-8 randomised 300 adults already on glimepiride to Trulicity® 1.5 mg or placebo for 24 weeks. ^[5] Total hypoglycemia was 2.37 events per participant-year on Trulicity® against 0.07 on placebo, and nobody had a severe episode. ^[5] It is the clearest single-trial picture of what adding Trulicity® to a sulfonylurea does.

AWARD-7 was an open-label, company-funded trial in 577 adults with stage 3–4 chronic kidney disease, all of whom also took mealtime insulin lispro. ^[6] Over 52 weeks, symptomatic hypoglycemia ran at 4.4 and 4.3 events per patient-year on Trulicity® 1.5 mg and 0.75 mg, against 9.6 on insulin glargine. ^[6] The comparison is with another insulin, so it shows Trulicity® caused fewer lows than glargine in that group, not that lows were rare: the Canadian table for the same study still shows symptomatic hypoglycemia in 40.5% to 48.1% of people on Trulicity®. ^[4]

Why the partner medicine sets the risk

What the labels support: dulaglutide raises insulin release in proportion to glucose and lowers glucagon, which is why it adds little risk on its own. ^[1] Insulin and sulfonylureas push glucose down whatever the level, so the combination carries the risk. The US label says lowering the sulfonylurea or insulin dose may reduce lows and leaves that to the prescriber; the EU summary adds that blood glucose self-monitoring is then needed, and Canada says it may become necessary. ^[1][3][4]

What is plausible but not measured for Trulicity®: the labels do not test whether eating less, nausea or vomiting lead to lows. NIDDK lists skipping or delaying meals, not eating enough carbohydrate, fasting for a procedure and being too unwell to eat or keep food down among general causes of low glucose in people on glucose-lowering medicines. ^[9] Reduced appetite is one of the most common Trulicity® reactions, so that link is worth raising with your prescriber if you use insulin or a sulfonylurea. ^[1]

General medical knowledge: NIDDK also names unusual physical activity, which can lower glucose for hours afterwards, and alcohol taken without food. ^[9]

When the shakes are not a low, and when insulin comes down too fast

Weakness, sweating, a racing heart and light-headedness overlap with other problems, so a meter reading at the time is the only way to know. MedlinePlus notes that many diabetes medicines do not cause lows at all, and that in people without diabetes low glucose can come from alcohol, severe heart, kidney or liver failure, or certain antibiotics and heart medicines. ^[7] Feeling faint from fluid loss after vomiting or diarrhoea is covered on the Trulicity® dizziness page.

The opposite risk matters for anyone moving from insulin to Trulicity®. Europe and Canada state that Trulicity® is not for type 1 diabetes or diabetic ketoacidosis and cannot replace insulin, and the EU summary reports ketoacidosis in insulin-dependent patients after insulin was stopped or reduced quickly. ^[3][4] The EU leaflet describes its signs as rapid weight loss, nausea or vomiting, a sweet smell on the breath, a sweet or metallic taste and an unusual smell to urine or sweat. ^[3] The EU summary describes a stepwise approach when insulin is reduced. ^[3]

Getting ready for a low

Before the first dose, the US Medication Guide wants a conversation with your provider about lows and how you would handle one, including whether you take insulin or a sulfonylurea. ^[2] The EU leaflet puts it the other way round: your doctor should tell you how to treat a low. ^[3] MedlinePlus advises checking your glucose whenever symptoms appear and keeping a source of fast-acting sugar with you, and NIDDK suggests teaching family, friends and coworkers when and how to give glucagon, and wearing a medical alert ID. ^[8][9] How much sugar to take and when to recheck belong to the plan your own care team gives you.

For driving, the EU summary says Trulicity® itself has no or negligible effect, but with a sulfonylurea or insulin it asks for precautions against lows behind the wheel, and the leaflet says not to drive or use machines if you notice any sign of one. ^[3] Canada gives the same advice. ^[4] MedlinePlus adds that if symptoms do not improve after a sugary snack, you should get a ride to the emergency room rather than drive yourself. ^[7] Illness can also upset glucose; MedlinePlus suggests asking your doctor in advance what to do if you get sick or develop a fever while on dulaglutide. ^[10]

Trulicity® is a registered trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Eli Lilly and Company.