As millions abandon New Year’s weight loss resolutions each year, a rapidly evolving landscape of medical interventions is offering new hope-and raising complex questions-for those struggling with obesity. The FDA recently approved the first daily pill version of Wegovy, joining previously available injectable medications like Ozempic and Mounjaro in the fight against weight gain. This article examines the efficacy and potential drawbacks of these drugs, alongside evolving research into optimal diets-including ketogenic, fasting, and time-restricted feeding-and the role of surgical interventions for more resistant cases.
Losing weight is a perennial New Year’s resolution, often made with enthusiasm but abandoned by September – another month filled with good intentions. But new medications and advancements are changing the landscape of weight management, offering potential solutions for those struggling to reach their goals.
Initially, injectable Ozempic gained attention, followed by Wegovy and Mounjaro. Now, the U.S. Food and Drug Administration (FDA) has recently approved the first daily pill for weight loss: an oral version of Wegovy. This new formulation offers the same effectiveness as the injection, but without the need for a shot. These medications can lead to significant and rapid weight loss, but they aren’t for everyone.
Currently, they are indicated for individuals with a Body Mass Index (BMI) of 30 or higher (indicating obesity), or a BMI of 27 or higher (indicating overweight) when accompanied by weight-related health conditions like diabetes, hypertension, or high cholesterol. However, some individuals with less weight to lose are using these drugs off-label, seeking an easier path to weight loss. This practice has drawn criticism from Svetlana Mojsov, a researcher whose work paved the way for these medications.
In an interview, Mojsov cautioned, “If one has to lose 15 kilos, they should do it in a healthy way, without medication. It’s not something trivial; it’s a medication that alters the overall balance of hormones in your body. It’s not good to play with this medication. It is safe, as long as it is used under medical control and with monitoring of tests to determine how it impacts other parameters.”
The effects of these medications are contingent on continued use. According to research, weight regain is common when the drugs are stopped, and the benefits to cardiovascular and metabolic health markers, such as cholesterol and blood pressure, can also reverse. A recent meta-analysis published in the journal The BMJ, which included 37 studies and over 9,300 participants, confirmed these findings. This underscores the importance of considering long-term maintenance strategies alongside medication.
The Foundation of Weight Management
Diet and exercise remain the cornerstones of maintaining a healthy weight. “The importance of a nutritional plan and exercise is fundamental and lifelong. It’s the basis of this lifestyle change, and all clinical trials of these drugs have been conducted in addition to nutrition and exercise,” says Dr. Cristóbal Morales, an endocrinologist at Vithas Sevilla Hospital, a member of the SEEDO board, and a researcher in clinical trials on semaglutide, the active ingredient in Ozempic and Wegovy. He emphasizes the importance of consulting a healthcare professional before starting medication to determine the best approach for individual health and long-term well-being.
Dr. Morales describes obesity as a “chronic, relapsing, and very complex” disease. “If you abandon treatment and return to your previous habits, the natural tendency is to regain weight.” Clinical trials are currently underway to explore different dosing schedules – minimal doses, alternating doses, or even discontinuing the medication while incorporating healthy habits – to determine if weight maintenance can be achieved. New oral medications and future developments in 2026 and 2027 aim to provide increasingly personalized treatment options.
Diets That Work
Research continues to explore the most effective diets for weight loss. A new study led by Dr. Francisco J. Tinahones, director of scientific research at IBIMA Plataforma BIONAND and head of the ‘Obesity, Diabetes and its Comorbidities: Prevention and Treatment’ group, sheds light on innovative nutritional strategies. Published in BMC Medicine, the study suggests that alternative diets – such as the ketogenic diet, modified alternate-day fasting, or early time-restricted feeding – may be significantly more effective for short-term weight loss than a traditional low-calorie diet.
Dr. Tinahones’ team conducted a randomized clinical trial lasting three months with 160 adults with obesity. This is one of the first studies to directly compare, under controlled conditions, the impact of different types of calorie-restricted diets: a classic low-calorie diet (3-4 meals spread throughout the day and balanced in macronutrients), the ketogenic diet (with a very low intake of carbohydrates), early time-restricted feeding (not eating breakfast) and late time-restricted feeding (not eating dinner), and modified alternate-day fasting (eating normally one day and very low-calorie the next, with no more than 300 kcal based on protein). The fasting and classic low-calorie groups followed a nutrient intake pattern based on the Mediterranean diet, and all groups in the study consumed the same number of calories per week, although their distribution varied in the case of fasting.
Alternate-day fasting is more effective for weight loss than traditional low-calorie diets, according to a Spanish study
Individuals following the ketogenic diet, modified alternate-day fasting, or early time-restricted feeding experienced significantly greater weight loss than those following a classic low-calorie diet, which served as the control group. “All participants had the same calorie restriction, but surprisingly, patients in the fasting groups had better adherence and achieved significant weight loss. This may be because it was easier for them to follow than when calorie restriction affects all four meals of the day,” explains Dr. Tinahones.
Participants in the modified alternate-day fasting group lost 3.14 kg more than those on the classic low-calorie diet. Similarly, those assigned to the ketogenic diet lost 3.78 kg more than the control group. However, all dietary interventions proved effective, as even the group following the classic low-calorie diet achieved an average weight loss of 8.4 kg.
Beyond body weight, the study also evaluated the effects on body composition. All diets induced a reduction in fat mass, but modified alternate-day fasting and late time-restricted feeding stood out as approaches that most reduced body fat, with modified alternate-day fasting showing the greatest impact in this parameter.
“Almost everyone lost more than 8 kilos in three months. Everyone improved, but the loss was greater in those who did intermittent fasting, which also had a better metabolic effect than the other diets. Blood pressure decreased, and improvements were seen in neurocognitive functions. When you lose weight, concentration, short-term memory, and long-term memory tests improve,” explains Dr. Tinahones.
Dr. Tinahones believes the success of fasting for weight loss is due to the fact that when you haven’t eaten for more than 12 hours, and you don’t have a glucose reserve, fats begin to be metabolized, and ketone bodies appear in the blood as fuel, which suppress appetite. “If I don’t have dinner, the next day there is no compensatory intake because these molecules in our body reduce our appetite. Many studies reflect that intermittent fasting is a good option for losing weight. The ketogenic diet cannot be maintained as a lifestyle in the long term and is not indicated in some patients with diseases, but intermittent fasting can be maintained over time,” he concludes.
New oral medications and future developments in 2026 and 2027 aim to achieve increasingly personalized treatment.
Dr. Inka Miñambres, a member of the SEEN obesity area, emphasizes that when trying to lose weight with diet, the proposed eating plan “should be adapted to each patient’s clinical characteristics and preferences, and should be planned to facilitate long-term adherence.” “In our environment, the Mediterranean diet should be promoted for its adaptation to our culture and its association with a reduction in the risk of numerous diseases, including cardiovascular disease, cancer, type 2 diabetes, and degenerative diseases,” she points out.
The problem with diets is that in severe obesity, they require a lot of willpower. A person can be on a strict diet for 3 months and lose 10 kilos, but if they have to lose 40, the consistency of a year is not easy, and patients end up getting bored. “That’s where these drugs come in, which fortunately are tremendously successful,” he says. But in his opinion, you should always start with a diet. “Any patient with excess weight who is motivated should be proposed a lifestyle change: a personalized, low-calorie diet. In case of repeated failure of dietary therapy, drugs should be used,” he says.
However, the nutritional strategy must be not only before, but also concurrent with the drugs. “What must be clear is that dietary habit modifications must always be present, regardless of whether they constitute the only treatment or are accompanied by diet, drugs, or even bariatric surgery,” warns Dr. Miñambres.
Furthermore, drugs, although very effective, do not work equally well in all people, so they are not a panacea. “We know that there are people who show almost no response to treatment, while there are others who respond more than expected. Although we do not know exactly who will respond, it is possible that in the future we will have pharmacogenetic data that will help us determine this response,” says the SEEN expert.
If you’ve gained a few kilos over the holidays, Dr. Tinahones recommends getting rid of that baggage to avoid accumulating because it’s difficult to get rid of 40-50 kilos later. “With any of the study strategies, those few kilos accumulated during the holidays have been lost in 3-4 weeks,” he assures.
Bariatric Techniques
In cases of more resistant obesity, even medications are sometimes not effective enough. A multidisciplinary team from the Clínica Universidad de Navarra published a study last December in the journal Obesity comparing the results of three types of interventions in 20,000 patients with obesity: bariatric surgery (tubular gastrectomy and gastric bypass), pharmacological treatments with GLP-1 receptor agonists (drugs from the Ozempic, Wegovy, or Mounjaro family), and lifestyle modifications (diet and exercise).
The research reveals that although GLP-1 agonists (liraglutide, semaglutide, tirzepatide) produce clinically significant weight loss, bariatric surgery remains the most effective strategy for reducing weight at least two years after the start of the surgical intervention, pharmacological treatment, or lifestyle change.
But when is bariatric surgery recommended? “It is indicated in patients with a BMI greater than 40 or in those with a BMI of 35 with comorbidities (cholesterol, diabetes, hypertension, joint problems). In BMIs lower than 30, only if the patient has type 2 diabetes that is not adequately controlled with medication,” explains Dr. Lucas Sabatella, a specialist in training at the Department of General and Digestive Surgery at the Clínica de Navarra and first author of the work.
In obese patients, using drugs like liraglutide and semaglutide, weight losses are “very modest. It is rare to lose more than 10% at maximum doses.” “With tirzepatide, the loss can reach 20%, but with surgery it can reach 40% of body weight,” says the expert, who assures that most of the patients who now arrive at the operating room have previously tried these medications without success.
In people with obesity, bariatric surgery continues to be the most effective strategy for weight loss, according to a study by the CUN
Midway between drugs and surgery is endoscopic bariatric surgery. The patient profile for this type of intervention is usually a person with mild or moderate overweight or obesity (BMI between 30 and 40) who has been trying to lose weight for years through diets, exercise, and increasingly, with pharmacological treatments, but without achieving stable results over time.
The advantages, compared to surgery, are that “it is reversible and modifiable. It is a minimally invasive procedure performed through the mouth and therefore does not require incisions or external scars. It is a reduction in stomach capacity internally without removing or cutting,” explains Dr. Gontrand López-Nava, director of the Endoscopic Bariatric Surgery Unit at HM Sanchinarro University Hospital. The expert assures that endoscopic bariatric surgery allows for remarkable weight loss, around 15–25%, with a rapid recovery and without incisions, “always within a structured medical program that includes nutritional follow-up and lifestyle changes.”
Dr. López-Nava sees daily patients who have tried obesity medications and who, for various reasons, opt for endoscopy: “From side effects to discontinuation of treatment and subsequent weight regain, for economic reasons, or simply because they need an alternative that does not depend on the chronic use of medication. More and more patients who come to the clinic have previously tried the new anti-obesity drugs. And in many cases they have worked at the beginning, but they are not always easy to maintain over time.”
To maintain the results after a treatment, of any type, Dr. Tinahones recommends changing 4 dietary patterns: avoid ultra-processed foods, reduce fatty products and refined sugars, and restrict alcohol. And don’t forget exercise: do 7,000 steps a day already has a favorable impact on health and do strength exercises for at least 30 minutes a day to strengthen legs and arms. But exercise alone does not compensate for intake; you have to reduce it. “It is very difficult to lose weight without effort,” concludes the expert.
