Foundayo™ and changes in mood

If you need help now

Thoughts of suicide, self-harm or not wanting to live need help today, not at the next appointment. In the US, call or text 988 or chat at 988lifeline.org; the line is free, confidential and open around the clock ^[12]. You can also call 911 or go to an emergency room. Outside the US, call your local emergency number. If someone has attempted suicide, call emergency services and do not leave them alone ^[10].

What the Foundayo™ documents say

Foundayo™ is a once-daily orforglipron tablet, a GLP-1 receptor agonist that its label does not describe as a peptide ^[1]. Its Warnings and Precautions cover the thyroid, pancreas, stomach, kidneys, low blood sugar, allergy, diabetic eye disease, gallbladder and anaesthesia, but not mood or suicidal thoughts ^[1]. No psychiatric reaction is listed in its adverse-reaction section ^[1].

The label gives 2026 as the year of first US approval, the same year the FDA completed its class review ^[1][3]. That review covered 91 placebo-controlled trials and a large insurance-claims study, and concluded that the evidence does not support a causal link between GLP-1 medicines and suicidal thoughts or behaviour ^[3]. The FDA asked for the existing warning to be removed from Saxenda®, Wegovy® and Zepbound® ^[3].

What the trials recorded

The two weight trials behind the label, ATTAIN-1 and ATTAIN-2, posted all serious events and any other event affecting at least 5% of a group. Some diabetes trials posted every event. Psychiatric entries are summarised below; the ACHIEVE trials used trial doses in type 2 diabetes.

What the trial data can and cannot show

• Anxiety, the only mood-related term common enough to reach the 5% list, was less frequent on every orforglipron dose than on placebo in ATTAIN-1 ^[6].
• Serious events such as suicidal thoughts or a suicide attempt occurred in single people, in both orforglipron and comparison groups. Numbers this small cannot show whether risk is raised or lowered ^[6][7][8][9].
• The registry tables give counts only; they do not describe who was affected, when, or what else was going on at the time.
• The FDA’s class-wide review is larger than any single orforglipron trial, but it was not specific to orforglipron ^[3].

Reasons mood can shift on Foundayo™

Supported by the label and Medication Guide: low blood sugar. Foundayo™ can cause it, especially with insulin or a sulfonylurea ^[1], and the Medication Guide names anxiety, irritability and mood changes among its signs ^[2]. MedlinePlus adds feeling cranky or nervous ^[11].

Plausible but not studied for orforglipron: poor sleep and physical discomfort. Stomach side effects are common early in treatment ^[1], and MedlinePlus lists sleeping problems among factors that can bring on depression ^[10].

General: big changes in eating, weight and routine can be stressful in their own right, and stressful life events are a recognised trigger for low mood ^[10]. No Foundayo™ study has measured this.

Other common causes of low mood

MedlinePlus lists many factors that can bring on depression ^[10]:

• Stressful life events such as job loss, divorce or bereavement, and social isolation.
• Alcohol and drug use.
• An underactive thyroid, cancer and long-term pain.
• Sleep problems.
• Some medicines, including steroids and beta-blockers.
• A family history of depression.

What the guidance says to do

The FDA advises patients to keep taking their medicine as prescribed, to discuss concerns with their clinician, and to report new or worsening depression, suicidal thoughts or unusual changes in mood or behaviour ^[3]. MedlinePlus says to contact a provider if low mood has affected work, school or family life for more than two weeks, if you have several symptoms of depression, or if you think a medicine is making you feel depressed, and not to change or stop any medicine without talking to them first ^[10].

If you have diabetes and use insulin or a sulfonylurea, checking your blood sugar when you feel suddenly anxious or irritable helps separate a low from a change in mood ^[2][11].

Points specific to Foundayo™

Tell your prescriber about any history of depression, anxiety or other mental health conditions before starting, and about any other medicines you take; the Medication Guide asks for a full list because Foundayo™ can affect how some medicines work ^[2].

Foundayo™ is raised in steps no sooner than every 30 days ^[1]. Recording your mood rating alongside each dose step makes it easier for you and your prescriber to see whether a change lines up with the medicine or with something else in your life.

Foundayo™ is a trademark of Eli Lilly and Company. Saxenda® and Wegovy® are registered trademarks of Novo Nordisk A/S; Zepbound® is a registered trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Eli Lilly and Company or Novo Nordisk.