Can I Take Glycine with Wegovy? A Clinical Review

What glycine is and what doses were studied

Glycine is a non-essential amino acid. The liver and kidneys use glycine, arginine and methionine to make about 1 g of creatine a day, and oral glycine is sold over the counter as a dietary supplement [3][4]. Drugs@FDA lists glycine in approved prescription irrigation and injectable products, such as glycine 1.5% irrigation solution (NDA 016784, approved in 1978); no oral glycine drug was found [3][4].

The doses used in human trials are far apart. A sleep study used 3 g before bedtime for three nights [2]. A dose-finding trial used glycine plus N-acetylcysteine (GlyNAC, 1:1) at 2.4, 4.8 or 7.2 g/day total for two weeks in 114 healthy older adults [5]. Schizophrenia trials used 30 to 60 g/day [6][7]. These are study doses, not recommended doses.

How semaglutide is handled in the body

Wegovy injection is given once weekly; the usual maintenance dose is 2.4 mg for weight reduction [1]. Semaglutide is broken down by proteolytic cleavage of its peptide backbone and beta-oxidation of its fatty acid side chain, not by CYP enzymes, and the label describes a very low potential for it to inhibit or induce CYP enzymes [1]. Its half-life is about a week, so the drug stays in the body for roughly five to seven weeks after the last 2.4 mg injection [1].

No human interaction studies of glycine with other common medicines, such as blood pressure, diabetes or hormone therapies, were found [2].

The oral-medicine note in the Wegovy label

The label says Wegovy delays gastric emptying and may affect absorption of oral medicines; it advises considering increased clinical or laboratory monitoring for oral drugs that have a narrow therapeutic index or that require clinical monitoring [1]. In clinical pharmacology trials with semaglutide 1 mg once-weekly injection, semaglutide did not affect the absorption of oral medicines to a clinically relevant degree [1]. Glycine is not among the medicines the label lists as tested [1].

The one clear absorption signal in the label is with the tablet form, where levothyroxine exposure rose 33% [1]. The injection can be given on the same day each week at any time of day, with or without meals [1].

Glycine's one drug-interaction signal: clozapine

In 19 treatment-resistant schizophrenia patients taking clozapine 400 to 1,200 mg/day, adding glycine 30 g/day for 12 weeks did not reduce symptoms, while patients on clozapine alone had a 35% fall in positive symptoms; the authors suggested glycine may interfere with clozapine's effect [6]. A separate placebo-controlled trial added 60 g/day for eight weeks in 30 adults and found no significant change in symptoms or thinking and no clinically significant worsening, but no benefit either [7]. Both doses are 10 to 20 times the 3 g sleep dose, and neither trial involved semaglutide.

Blood sugar: what each side does

In a single-dose study, nine healthy people were tested on four occasions: 1 mmol glycine per kg lean body mass, 25 g glucose, both together, or water [9]. Glycine alone slightly raised serum insulin. Given with glucose, it cut the plasma glucose area response by more than half compared with glucose alone, while the insulin area response did not differ significantly; the authors suggested glycine prompts release of a gut hormone that potentiates insulin's effect on glucose removal from the circulation [9]. That is one small study of single doses in people who were not taking semaglutide.

Wegovy lowers blood glucose, and the label says hypoglycemia risk rises when it is used with insulin or an insulin secretagogue such as a sulfonylurea; when starting Wegovy, the label says to consider reducing the dose of those medicines [1]. In the weight trial in adults with type 2 diabetes and a BMI of 27 or higher, glucose below 54 mg/dL occurred in 6.2% of those on Wegovy 2.4 mg versus 2.5% on placebo, and the risk was higher with a sulfonylurea [1]. For patients with diabetes, the label says to monitor blood glucose before starting and during treatment [1].

Sleep: what the 2012 trial measured

Bannai et al. cut healthy volunteers' sleep to about 25% less than usual for three nights and gave 3 g of glycine or placebo before bed [2]. Next-day fatigue on a visual analog scale fell significantly, sleepiness tended to fall, and psychomotor vigilance improved [2]. Plasma melatonin was unchanged [2]. This was a sleep-restriction study in healthy volunteers, not a treatment trial in insomnia, and the participants were not taking semaglutide. A review from the same research group describes a fall in core body temperature and a rise in cutaneous blood flow in rats given oral glycine, which the authors link to sleep onset [10].

Side effects on each side

The Wegovy label lists nausea (44% versus 16% on placebo), diarrhea (30% versus 16%), vomiting (24% versus 6%) and constipation (24% versus 11%) among the most common reactions in the pooled 2.4 mg injection trials [1]. GlyNAC was described as safe and well tolerated in both a 24-person, 16-week trial and a 114-person, two-week trial, and neither report gives a side-effect list for glycine on its own [8][5].